Silvia Degli Esposti

Hepatitis B in Pregnancy: Challenges and Treatment

Hepatitis B virus (HBV) during pregnancy presents unique management challenges. Varying aspects of care must be considered, including the effects of HBV on maternal and fetal health, effects of pregnancy on the course of HBV infection, treatment of HBV during and after pregnancy, and prevention of perinatal infection. Antiretroviral therapy has not been associated with increased risk of birth defects or toxicity, but despite studies designed to elucidate the drug efficacy and safety in affected individuals and the developing fetus, recommendations are inconclusive. Clinicians and patients must make individualized decisions after carefully evaluating the risks and benefits summarized in this article.

Gene expression of transforming growth factor β1 and extracellular matrix proteins in murine Schistosoma mansoni infection

BACKGROUND/AIMS The study of Schistosoma-induced hepatic fibrosis in murine Schistosoma mansoni infection has elucidated the nature of hepatic fibrosis in humans. In the present study, fibrogenic gene expression was determined in murine S. mansoni infection during primary infection, after chemotherapy with praziquantel, and during secondary infection. METHODS Both histomorphometric analysis and Northern blot profiles were performed. RESULTS Histomorphometric analysis of granulomatous inflammation showed smaller hepatic fibrotic granulomata after chemotherapy and during secondary infection. Albumin gene expression remained relatively constant throughout primary infection, chemotherapy, and secondary infection. Fibronectin gene expression in primary infection was comparable with the level observed in noninfected mice and was reduced by chemotherapy. Reinfection resulted in augmented expression levels equal to primary infection levels. Osteonectin gene expression was active in primary infection, was reduced by chemotherapy, and was actively reexpressed in secondary infection. Interstitial matrix macromolecules, types I and III collagen, and basement membrane collagen showed high levels of gene expression in primary infection, were virtually terminated by chemotherapy, and were reexpressed on reinfection. The gene expression of transforming growth factor beta 1, a major, fibrogenic cytokine, paralleled collagen expression. CONCLUSIONS Chemotherapy of schistosomiasis initiated a dramatic decrease in steady-state messenger RNA levels of major proteins associated with fibrosis; reinfection resulted in a reexpression of these genes.

TGF-β isoforms in alcoholic liver disease

Abstract: The increased deposition of extracellular matrix proteins in the liver is a key factor in the morbidity and mortality of alcoholic liver disease (ALD). This increased fibrosis may be due to a superabundance of profibrogenic factors such as transforming growth factor-β (TGF-β). The original peptide is now called TGF-β1, and two other isoforms have been recognized in humans (TGF-β2 and TGF-β3). It was the aim of the present study to determine the expression of the TGF-β isoforms in different stages of ALD. Thirty patients with ALD had percutaneous liver biopsies performed for diagnostic purposes. They were grouped by clinical findings and by liver histology into four groups: I, steatosis; II, fibrosis; III, hepatitis; and IV, cirrhosis. An unused portion of each biopsy sample was used to evaluate the gene expression of TGF-β1, TGF-β2, and TGF-β3 by reverse transcription polymerase chain reaction (RT-PCR). The expression of all isoforms from patients was significantly greater than their expression in controls. No significant correlation was determined between TGF-β isoform expression and liver function test results. When the different isoforms were grouped by histology, increased expression with more severe disease was found; however, differences existed among the isoforms. In ALD, all TGF-β isoforms were increased and their expression was significantly greater in patients with more active and advanced disease. RT-PCR is an effective method for evaluating gene expression in clinical samples which often provide a limited amount of tissue.

Menstrual cycle changes in women with inflammatory bowel disease: a study from the ocean state Crohn's and colitis area registry.

Background:The effect of the inflammatory bowel diseases (IBD) on menstrual function is largely unknown. The aims of this study were to determine whether changes in menstrual function occur in the year before IBD diagnosis or in the initial years after diagnosis. Methods:Women aged 18 years and older in the Ocean State Crohns and Colitis Area Registry with at least 2 years of follow-up were eligible for this study. All patients were enrolled within 6 months of IBD diagnosis and followed prospectively. Menstrual cycle characteristics were retrospectively assessed. To assess for changes over time, general linear models for correlated data were used for continuous outcomes, and generalized estimating equations were used for discrete outcomes. Results:One hundred twenty-one patients were studied. Twenty-five percent of patients experienced a change in cycle interval in the year before IBD diagnosis and 21% experienced a change in the duration of flow. Among women with dysmenorrhea, 40% experienced a change in the intensity of their menstrual pain and 31% experienced a change in its duration. Overall cycle regularity increased over time. Quality of life was significantly lower in women without regular cycles across all time points. Conclusions:Changes in menstrual function occur frequently in the year before IBD diagnosis; therefore, screening for menstrual irregularities should be considered in women with newly diagnosed IBD. Patients can be reassured that cycles typically become more regular over time.

2 Pregnancy Outcomes Amongst Mothers With Inflammatory Bowel Disease Exposed to Systemic Corticosteroids: Results of the PIANO Registry

Introduction: IBD in the mother is associated with higher rates of adverse pregnancy outcomes. However, long-term effects of maternal IBD on childhood growth and development are not known. The aim of this study was to determine the impact of IBD medication exposure in utero on newborn developmental milestones. Methods: We created a prospective cohort of pregnant women at 30 US IBD centers to follow patients through pregnancy and first four years of a childs life. We ascertained IBD medications and disease activity during gestation, complications of pregnancy and delivery, and achievement of developmental milestones. Patients were classified by exposure to drugs taken between conception and delivery: 6MP/Azathioprine (Group A), infliximab, adalimumab, certolizumab (Group B), combination therapy (Group AB). We compared these groups to women who did not take any Group A or B drugs. Developmental milestones achieved by the infant, based on Denver Childhood Developmental Score, were measured by the mother at months 4, 9 and 12 and by the validated Ages and Stages Questionnaire at 1,2,3 and 4 years of age. Follow up is ongoing. Results: 1289 women are enrolled in the study as of Nov 12 2013: 1097 have completed pregnancy, 1039 with live births. There were 215 live births in Group A, 364 in Group B, 137 in Group AB and 323 to unexposed mothers. When compared to the unexposed infants, infants in Group A, B and AB always had equivalent or better achievement of milestones. These results were unchanged when controlled for maternal income and education level. Table 1 lists the milestones in which the exposed infants had better outcomes that the unexposed. Conclusions: Infants with in utero exposure to immunomodulator and biologic therapy did not exhibit developmental delay compared to infants not exposed to these agents, controlling for preterm birth. Overall, developmental scores were similar between exposed and unexposed infants, and scores of exposed infants were slightly higher in some categories. Significant Differences in Developmental Milestones by Drug Exposure

Effect of vitamin E on reoxygenation injury experienced by isolated rat hepatocytes

The pathogenic role of lipid peroxidation in the reperfusion injury of the liver is still controversial. This study was performed to determine whether the damage caused by oxygen free radicals during reoxygenation in perfused rat hepatocytes is related to lipid peroxidation. Superoxide anion was detected by lucigenin-enhanced chemiluminescence. Lipid peroxidation and cell injury were assessed by the release of malondialdehyde and lactic dehydrogenase. Upon reoxygenation following 2.5 h of anoxia, isolated hepatocytes generated considerable amount of O2-. Following O2- formation, a significant increase in malondialdehyde release was measured. Cell injury was temporally delayed relative to O2- generation, but preceded the occurrence of a significant lipid peroxidation. Treatment with Vitamin E abolished lipid peroxidation but had no effect upon superoxide anion formation and cell injury. These results suggest that in perfused rat hepatocytes non-peroxidative mechanisms are more important than peroxidative mechanisms in the pathogenesis of the early phases of reoxygenation injury.

Effect of Ischemia-Reperfusion on Heat Shock Protein 70 and 90 Gene Expression in Rat Liver: Relation to Nutritional Status

Heat shock proteins are intracellular proteinsassociated with a generalized response of cells tostress. The purpose of this study was to assess RNAlevels of heat shock protein 70 and 90 in fed or fasted rat livers during ischemia-reperfusion.Northern blot analysis of heat shock proteins wasperformed. Adenosine triphosphate and glutathione wereassessed. In baseline conditions, livers of fasted ratsshowed a twofold increase in mRNA for both heat shockproteins and 38% and 43% reductions in adenosinetriphosphate and glutathione, respectively, whencompared with organs from fed rats. After ischemia,livers of fasted rats presented a twofold decrease inheat shock protein mRNA, while no changes were observedin livers of fed rats; reduced glutathione and adenosinetriphosphate decreased 55% and 50% in fasted livers and 25% and 20% in fed organs,respectively. After 120 min of reperfusion, heat shockprotein mRNA rose threefold in fasted livers, while aslight decrease was observed in the fed group; reduced glutathione and adenosine triphosphate returnedto 65% and 70% of baseline values in fasted livers and85% and 90% in fed organs, respectively. In conclusion,the nutritional status affects heat shock protein expression determined by reperfusion. Thereduced antioxidant status leading to increasedoxidative stress could be the mechanism underlying thephenomenon.

Body image dissatisfaction in patients with inflammatory bowel disease.

Background:Despite the fact that the inflammatory bowel diseases (IBD) and their treatments may affect physical appearance, the effect of IBD on body image is poorly understood. The aims of this study were to determine whether body image dissatisfaction (BID) changes over time in patients with IBD and to examine the demographic and disease-related variables associated with decreased body image. Methods:Adults aged 18 and above in the Ocean State Crohns and Colitis Area Registry with at least 2 years of follow-up were eligible for this study. All patients were enrolled within 6 months of IBD diagnosis and followed prospectively. BID was assessed using a modified version of the Adapted Satisfaction With Appearance questionnaire. Total Adapted Satisfaction With Appearance scores and 2 subscores were calculated. To assess for changes over time, general linear models for correlated data were used for continuous outcomes, and generalized estimating equations were used for discrete outcomes. Results:Two hundred seventy-four patients were studied. BID was found to be stable over time among men and women with IBD despite overall improvements in disease activity. No differences were found in BID according to IBD subtype. Female gender, greater disease activity, higher symptom burden, longer duration of steroid use, dermatologic and musculoskeletal manifestations of IBD, and ileocolonic disease location among patients with Crohns disease were associated with greater BID. Greater BID was associated with lower health-related quality of life. Conclusions:BID remains stable in an incident cohort of IBD despite improved disease activity and is associated with lower health-related quality of life.

Gastroenterology Consultations in Pregnancy

BACKGROUND Training in gastrointestinal (GI) disorders in pregnancy is required for all gastroenterology fellows. Nevertheless, the actual role of the gastroenterologist in the management of pregnant patients is unknown. Establishing the characteristics of GI consultations in pregnancy can help focus trainee education and prepare gastroenterologists for future practice. The purpose of this study was to determine the indications for consultations in pregnancy and the gastroenterologists role in the evaluation and management of the pregnant patient. METHODS A chart review was performed of all consecutive outpatient GI consultations for pregnant women at a high-volume obstetrics hospital over a 3-year period. Referring source, patient characteristics, indication(s) for consultation, diagnosis(es), change in management after consultation, and need for follow-up were recorded. RESULTS We reviewed 370 charts. The mean age (±standard deviation [SD]) at referral was 28.7 years ± 6.5, and mean weeks of gestation (±SD) was 21.3 ± 8.8. Obstetrician/gynecologists requested most consultations (70.1%). New GI symptoms arising in pregnancy comprised 35.4% of consultations, and worsening of a preexisting GI disorder comprised 24.4%. The most common indications for consultation were viral hepatitis (20.2%), nausea and vomiting (18.9%), and nonspecific abdominal pain (13.5%). The most common diagnoses were acute or chronic viral hepatitis (17.8%), hyperemesis gravidarum (15.1%), gastroesophageal reflux disease (14.3%), and constipation (13.0%). Consultation changed the diagnosis in 25.1% of patients and changed management in 78.6%. Follow-up was required in 77.3% of cases during pregnancy and 37.8% postpartum. CONCLUSIONS GI consultation in pregnancy is sought more frequently for the evaluation and management of GI disorders not unique to pregnancy than for pregnancy-unique disorders. Although GI consultation changed the diagnosis in a minority of cases, it changed management in the majority. Gastroenterologists should be familiar with the most common indications for consultation in pregnancy and be prepared to evaluate and manage pregnant women with GI disorders.

Meeting the Need for Women's Health Training in Gastroenterology: Creation of a Women's Digestive Disorders Program at Brown University

BACKGROUND Despite training requirements, knowledge and self-efficacy in womens health issues remain inadequate in many fields. In gastroenterology, nearly 60% of patients are women, and many disorders are more common in women. Adequate training in gastrointestinal (GI) womens health is, therefore, critical for gastroenterologists. OBJECTIVES (1) To create a core faculty in GI womens health, (2) to develop a GI womens health curriculum, (3) to provide didactic education and clinical experiences in GI womens health, (4) to produce self-efficacy in the evaluation and management of GI womens health issues, and (5) to develop academic gastroenterologists focused on GI womens health. METHODS We assembled a multidisciplinary group of GI womens health experts dedicated to training and mentoring GI fellows. We also held focus groups to determine the unmet needs in the management of the GI health of female patients in our community. Results from this needs assessment formed the foci of our program. In 2002, we introduced a 2-month rotation in GI womens health. Then, in 2005, we introduced a 3-year womens health pathway for trainees committed to academic careers. RESULTS Between 2002 and 2008, 13 fellows who participated in the rotation have graduated from the Brown GI fellowship program, and 1 has completed the track. Satisfaction with the program is high. Postgraduation survey results show that >80% of graduates who participated in the rotation feel prepared to evaluate and treat GI disorders in pregnancy, and nearly 65% feel prepared to address general GI womens health issues. All respondents report the GI womens health rotation provided training that was otherwise not addressed during fellowship. CONCLUSIONS A training experience in GI womens health can be created using local resources and expertise. Gastroenterologists with this training feel prepared to evaluate and manage the spectrum of womens health issues encountered in practice.