There are preliminary data demonstrating a direct effect of HIV o

There are preliminary data demonstrating a direct effect of HIV on the fibrogenic process through the binding of gp120 to CCR5 receptors on Ku-0059436 mw hepatic stellate cells, the principal fibrogenic cell type in the liver [32–33] which triggers an increased expression of collagen and inflammatory chemokines. Additional data suggest that microbial translocation [34] plays a role

in accelerating liver fibrosis through toll-like receptor (TLR) signalling [35] and HIV may have a direct role through suppression of a major transcription factor in fibrogenesis (PPARγ). No RCT evidence exists addressing the HBV DNA level at which anti-HBV treatment should be commenced in HBV/HIV-infected individuals. The choice of >2000 IU/mL is based on indirect data: i) the level of HBV DNA is proportional to the risk of cirrhosis and HCC in observational studies in monoinfection [8,36–39]; buy Epacadostat ii) the degree

of HBV viral suppression achieved during treatment is an important determinant in reducing progression to cirrhosis, liver failure, HCC and need for liver transplantation [8,40]; iii) prolonged low level viraemia may be associated with progressive liver damage in HBV-monoinfection [37] and; iv) levels of HBV DNA 2000–20 000 IU/mL may be associated with a histological indication for treatment. We recommend TDF/FTC as part of a fully suppressive ART combination should be given to all patients where HBV treatment is deemed necessary (1C). We suggest adefovir or 48 weeks of PEG-IFN are alternative options in patients unwilling or unable to receive TDF/FTC as part of a fully suppressive ART combination but requiring HBV therapy (2C). We suggest PEG-IFN is only used in HBsAg-positive patients Casein kinase 1 with a repeatedly raised ALT, low HBV DNA (<2 × 106 IU/mL), and minimal fibrosis, irrespective of HBeAg antigen status (2D). Lack of HBV DNA response (reduction to <2000 IU/mL at 12 weeks) should prompt discontinuation. Repeat testing should be performed 3-monthly to observe the presence of seroconversion (2C).

Where ART is not indicated for HIV, and the CD4 count is ≥500 cells/μL, the optimum strategy is uncertain: to use agents with exclusive HBV and no HIV activity (i.e., PEG-IFN and adefovir) so that HIV resistance is not induced, or earlier initiation of ART. Seven drugs are available with HBV activity: pegylated interferon (PEG-IFN), lamivudine (3TC), emtricitabine (FTC), adefovir (ADV), entecavir, telbivudine and tenofovir (TDF). Four have additional HIV activity (3TC, FTC, TDF and entecavir) and two are only active against HBV at licensed doses (PEG-IFN, ADV). There is conflicting evidence on whether telbivudine exerts activity against HIV. Entecavir and tenofovir are recommended first-line therapies for HBV monoinfection and have demonstrated high efficacy with low rates of resistance and a favourable safety profile. Both are safe in patients with decompensated liver disease.

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