Chronic hepatitis B is globally prevalent and is a major cause of cirrhosis and hepatocellular carcinoma. Despite immunoprophylaxis against hepatitis B in pregnancy, perinatal transmission still occurs in at least 10% of the children born to a mother with high level of viremia. Decisions regarding hepatitis B therapy during pregnancy must take into account the benefits and safety for both the mother and the unborn baby. In this review, we summarize the current treatment options for chronic hepatitis B with a focus on management during pregnancy and the evidence-based strategies to prevent vertical transmission of hepatitis B virus (HBV).
GNAS mutations leading to constitutively active stimulatory G protein alpha-subunit (Gsα) cause different tumors, fibrous dysplasia of bone, and McCune-Albright syndrome, which are typically not associated with short stature. Enhanced signaling of the parathyroid hormone/parathyroid hormone-related peptide receptor, which couples to multiple G proteins including Gsα, leads to short bones with delayed endochondral ossification. It has remained unknown whether constitutive Gsα activity also impairs bone growth. Here we generated mice expressing a constitutively active Gsα mutant (Gsα-R201H) conditionally upon Cre recombinase (cGsα mice). Gsα-R201H was expressed in cultured bone marrow stromal cells from cGsα mice upon adenoviral-Cre transduction. When crossed with mice in which Cre is expressed in a tamoxifen-regulatable fashion (CAGGCre-ER™), tamoxifen injection resulted in mosaic expression of the transgene in double mutant offspring. We then crossed the cGsα mice with Prx1-Cre mice, in which Cre is expressed in early limb-bud mesenchyme. The double mutant offspring displayed short limbs at birth, with narrow hypertrophic chondrocyte zones in growth plates and delayed formation of secondary ossification center. Consistent with enhanced Gsα signaling, bone marrow stromal cells from these mice demonstrated increased levels of c-fos mRNA. Our findings indicate that constitutive Gsα activity during limb development disrupts endochondral ossification and bone growth. Given that Gsα haploinsufficiency also leads to short bones, as in patients with Albright's hereditary osteodystrophy, these results suggest that a tight control of Gsα activity is essential for normal growth plate physiology.
Nearly 50% of the abstracts presented at major gastroenterology conferences in the USA are published as full manuscripts 5 years after the conference. Further studies are needed to assess why so many abstracts are not published.
Autoimmune hepatitis (AIH) is an autoimmune liver disease characterised by the presence of autoantibodies including antinuclear antibodies, anti-smooth muscle antibody and hypergammaglobulinaemia. Systemic lupus erythematosus (SLE) is a systemic disease that can affect multiple organs. Coexistence of AIH and SLE as an overlap syndrome occurs in about 1%–2.6% of the AIH cases. Since both conditions share common autoimmune features, their coexistence can pose a diagnostic dilemma which can result in a delay in treatment. We present here a challenging case of a middle-aged woman with AIH in remission who later developed new-onset fatigue, pleural effusion and splenomegaly.
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