Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study.

The aim of this multicenter study was to assess the present risk of fetal complications and the inherent risk factors in pregnant women with lupus nephritis. Seventy-one pregnancies in 61women (59 Caucasians and 2 Asians) with lupus nephritis were prospectively followed between October 2006 and December 2013. All patients received a counselling visit within 3 months before the beginning of pregnancy and were followed by a multidisciplinary team. At baseline mild active nephritis was present in 15 cases (21.1%). Six pregnancies (8.4%) resulted in fetal loss. Arterial hypertension at baseline (P = 0.003), positivity for lupus anticoagulant (P = 0.001), anticardiolipin IgG antibodies (P = 0.007), antibeta2 IgG (P = 0.018) and the triple positivity for antiphospholipid antibodies (P = 0.004) predicted fetal loss. Twenty pregnancies (28.2%) ended pre-term and 12 newborns (16.4%) were small for gestational age. Among the characteristics at baseline, high SLE disease activity index (SLEDAI) score (P = 0.027), proteinuria (P = 0.045), history of renal flares (P = 0.004), arterial hypertension (P = 0.009) and active lupus nephritis (P = 0.000) increased the probability of preterm delivery. Odds for preterm delivery increased by 60% for each quarterly unit increase in SLEDAI and by 15% for each quarterly increase in proteinuria by 1 g per day. The probability of having a small for gestational age baby was reduced by 85% in women who received hydroxychloroquine therapy (P = 0.023). In this study, the rate of fetal loss was low and mainly associated with the presence of antiphospholipid antibodies. Preterm delivery remains a frequent complication of pregnancies in lupus. SLE and lupus nephritis activity are the main risk factors for premature birth. Arterial hypertension predicted both fetal loss and preterm delivery. Based on our results the key for a successful pregnancy in lupus nephritis is a multidisciplinary approach with close medical, obstetric and neonatal monitoring. This entails: a) a preconception evaluation to establish and inform women about pregnancy risks; b) planning pregnancy during inactive lupus nephritis, maintained inactive with the lowest possible dosage of allowed drugs; c) adequate treatment of known risk factors (arterial hypertension, antiphospholipid and antibodies); d) close monitoring during and after pregnancy to rapidly identify and treat SLE flares and obstetric complications.

G protein-mediated signal transduction is affected in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by severe intraepatic cholestasis. Pruritus often occurs during the course of the illness. We designed a study aimed at assessing whether pruritus is associated with dysfunction of signal transduction. Seventeen female patients affected by PBC were enrolled into the study and divided in two groups according to severity of liver disease. Leukocytes were isolated from peripheral blood and Gi, Go and Gs protein expressions were evaluated by western blotting, while G protein function was assessed by measuring cyclic adenosine phosphate formation. The expression of all types of G proteins was increased in leukocytes of PBC patients. The basal adenylate activity was significally higher than control in patients with less severe liver disease, while it was lower than normal in those with severe liver disease. Incubation of patient leukocytes with guanosine triphosphate-gamma-S and Gs protein activators failed to enhance cAMP production, while N-formyl-met-leu-phe was more effective in reducing cAMP production. The expression of all G proteins was non-selectively increased in PBC leukocytes, while adenylate cyclase activity was significantly modified. However, the observed changes in G proteins expression and in adenylate cyclase activity are not related to the presence of pruritus.

Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial.

OBJECTIVE: To assess the incidence, cofactors, and excess risk of development of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, attributable to tamoxifen in women. DESIGN: Prospective, randomised, double blind, placebo controlled trial. SETTING AND PARTICIPANTS: 5408 healthy women who had had hysterectomies, recruited into the Italian tamoxifen chemoprevention trial from 58 centres in Italy. INTERVENTION: Women were randomly assigned to receive tamoxifen (20 mg daily) or placebo for five years. MAIN OUTCOME MEASURE: Development of non-alcoholic fatty liver disease in all women with normal baseline liver function who showed at least two elevations of alanine aminotransferase (> or = 1.5 times upper limit of normal) over a six month period. RESULTS: During follow up, 64 women met the predefined criteria: 12 tested positive for hepatitis C virus, and the remaining 52 were suspected of having developed non-alcoholic fatty liver disease (34 tamoxifen, 18 placebo)--hazard ratio = 2.0 (95% confidence interval 1.1 to 3.5; P = 0.04). In all 52 women ultrasonography confirmed the presence of fatty liver. Other factors associated with the development of non-alcoholic fatty liver disease included overweight (2.4, 1.2 to 4.8), obesity (3.6, 1.7 to 7.6), hypercholesterolaemia (3.4, 1.4 to 7.8), and arterial hypertension (2.0, 1.0 to 3.8). Twenty women had liver biopsies: 15 were diagnosed as having mild to moderate steatohepatitis (12 tamoxifen, 3 placebo), and five had fatty liver alone (1 tamoxifen, 4 placebo). No clinical, biochemical, ultrasonic, or histological signs suggestive of progression to cirrhosis were observed after a median follow up of 8.7 years. CONCLUSIONS: Tamoxifen was associated with higher risk of development of non-alcoholic steatohepatitis only in overweight and obese women with features of metabolic syndrome, but the disease, in both the tamoxifen and the placebo group, after 10 years of follow up seems to be indolent.