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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.

The gastrointestinal tract undergoes dramatic modifications during pregnancy. Heartburn, nausea, abdominal cramps, and altered bowel habits are the most common gastrointestinal symptoms of pregnant women. However, it may be a challenge to distinguish among functional symptoms and the onset of diseases that require immediate medical attention. The differential diagnosis must include diseases specific to pregnancy as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, and preeclampsia.

With universal HIV testing prior to or early in pregnancy, early and effective antiretroviral therapy for all pregnant women, scheduled cesarean delivery if indicated, and antiretroviral therapy for the infant, as well as effective pre- and postconception counseling, HIV-infected women can have healthy and successful pregnancies.

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 Crohn's 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.

Hepatitis C (HCV) is an indolent and often fatal disease affecting four million Americans commonly associated with low socio-economic status. We assessed its prevalence in a sample of 334 consecutively admitted middle class substance abusers in a private urban hospital, and ascertained risk factors for its transmission. We found that the point prevalence rate for HCV was 27.7% among all substance abusers, and 76.7% among intravenous drug users. Using logistic regression, we found risk factors associated with HCV were intravenous drug use, needle sharing, prior liver disease, opioid dependence, HIV infection, and benzodiazepine dependence. Not found to increase infective risk were lower social class, male gender, African-American race, male homosexuality, unemployment, and the absence of private health insurance. Multiple viral genotype types were identified in this sample, suggesting diverse sources of transmission in the sample. This study documents an epidemic of HCV in an American middle class...

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-beta (TGF-beta). The original peptide is now called TGF-beta 1, and two other isoforms have been recognized in humans (TGF-beta 2 and TGF-beta 3). It was the aim of the present study to determine the expression of the TGF-beta 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-beta 1, TGF-beta 2, and TGF-beta 3 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-beta 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-beta 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.

Heat shock proteins are intracellular proteins associated with a generalized response of cells to stress. The purpose of this study was to assess RNA levels of heat shock protein 70 and 90 in fed or fasted rat livers during ischemia-reperfusion. Northern blot analysis of heat shock proteins was performed. Adenosine triphosphate and glutathione were assessed. In baseline conditions, livers of fasted rats showed a twofold increase in mRNA for both heat shock proteins and 38% and 43% reductions in adenosine triphosphate and glutathione, respectively, when compared with organs from fed rats. After ischemia, livers of fasted rats presented a twofold decrease in heat shock protein mRNA, while no changes were observed in livers of fed rats; reduced glutathione and adenosine triphosphate decreased 55% and 50% in fasted livers and 25% and 20% in fed organs, respectively. After 120 min of reperfusion, heat shock protein mRNA rose threefold in fasted livers, while a slight decrease was observed in the fed group; reduced glutathione and adenosine triphosphate returned to 65% and 70% of baseline values in fasted livers and 85% and 90% in fed organs, respectively. In conclusion, the nutritional status affects heat shock protein expression determined by reperfusion. The reduced antioxidant status leading to increased oxidative stress could be the mechanism underlying the phenomenon.

Oxidative stress, with reactive oxygen intermediate formation, may represent a common mechanism by which liver injury is induced by diverse etiologies. Oxidative stress enhances nuclear factor kappa B (NF-kappa B) activity, and NF-kappa B activity has been shown to enhance the expression of cytotoxic cytokines. Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice. This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of alpha-tocopherol. Alpha-tocopherol treatment of the mice given the CCl4 also reduced the NF-kappa B binding to levels approaching those found in normal mice. In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced NF-kappa B binding and an increase in tumor necrosis factor-alpha (TNF-alpha) messenger RNA levels. Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-kappa B binding activity in comparison with the binding of normal livers. These data demonstrate that abolishing acute hepatic injury with alpha-tocopherol, a free radical scavenger, also eliminated increased NF-kappa B binding. It is tempting to speculate that enhanced NF-kappa B expression caused by free radical production/oxidative stress may modulate liver injury, perhaps through an effect on cytotoxic cytokine synthesis.

Molecular biological investigations have become a predominant methodology applied to the study of alcohol-induced liver disease. The enzymatic pathways responsible for ethanol metabolism, and their genetic as well as environmental control, have become the focus of detailed investigation. More recently, the significance of cytokines in the pathogenesis of alcohol-induced liver disease has also become a major area of speculation. This review focuses on the advances made in studies of two important enzymes responsible for alcohol metabolism, alcohol dehydrogenase and aldehyde dehydrogenase, as well as the investigation of the proinflammatory and profibrogenic cytokines involved in the process of hepatic fibrogenesis. The quality and quantity of new discoveries made in the field of alcohol-induced liver disease is impressive, especially when one realizes that molecular biological approaches have been employed in this area for only 15 years. However, in most cases the studies have been predominantly descriptive, with little direct relevance to the therapeutics of alcoholism and alcohol-induced organ injury. Because the groundwork has been laid, one hopes that the next 15 years will rectify this failure.

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 histomorphometeric 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 β1, 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.

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 gastroenterologist's role in the evaluation and management of the pregnant patient.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.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.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.

Hyperemesis gravidarum is severe nausea and vomiting during pregnancy leading to dehydration, nutrition deficiency, and fetal morbidity and mortality. Treatment must maintain fluid and electrolyte balance and caloric intake. Parenteral nutrition is often attempted; however, complication rates are high. Nutrition via nasoenteric and percutaneous endoscopic gastrostomy tubes is limited by poor patient tolerance, tube dislodgement, and altered anatomy in pregnancy.Women with hyperemesis gravidarum who failed standard therapy were offered jejunostomy. All patients underwent surgical jejunostomy in the second trimester. Isotonic tube feeds were administered to a goal caloric factor calculated by the Harris-Benedict equation with a correction added for pregnancy. Patients were monitored until delivery.Five women underwent jejunostomy placement at our institution between 1998 and 2005. One patient underwent jejunostomy placement twice for consecutive pregnancies. The mean body weight loss from prepregnancy was 7.9% (range, 4.0%-15.9%). Patients underwent jejunostomy placement between 12 and 26 weeks of gestation (median 14 weeks). Twelve to 16 Fr catheters were placed in the proximal jejunum. Maternal weight gain occured in 5 of 6 pregnancies. The mean duration of tube placement was 19 weeks (range, 8-28 weeks). All pregnancies ended with term deliveries (range, 36-40 weeks of gestation). The mean infant birth weight was 2885 g (range, 2270-4000 g). Tube-related complications were limited to dislodgement in 2 patients in the third trimester. No cases of infection, bleeding, or preterm labor occured.Feeding via jejunostomy is a potentially safe, effective, and well-tolerated mode of nutrition support therapy in hyperemesis gravidarum.

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 O 2− . Following O 2− formation, a significant increase in malondialdehyde release was measured. Cell injury was temporally delayed relative to O 2− generation, but preceded the occurence 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.

The relationship between Ito cells and hepatic fibrogenesis has been investigated in an experimental model: intraperitoneal injection of heterologous serum in rats leads to the appearance of fibrous septa within 5 weeks. Groups of rats were sacrificed at various intervals (from 2.5 to 20 weeks), saline-injected rats being used as controls. Liver fragments were prepared for light and electron microscopy and determination of hydroxyproline. Ito cells were identified by defined morphological criteria on 1 micron sections. The volume density (VD) of Ito cells and fibrous septa, and the Ito cell index were determined. Ito cells represent a very relevant component of early septa. In later stages, the VD of cells with morphological features of Ito cells falls to very low values. This might be related to modulation of Ito cells to fibroblasts. The increase of tissue hydroxyproline is delayed with respect to the peak VD of septal Ito cells, actually corresponding to the fall in the VD of septal Ito cells. The striking increase in the VD of total Ito cells cannot be related to a theoretically possible increase in the volume of single Ito cells, as VD always parallels the Ito cell index. These data suggest a hyperplastic reaction, possibly associated with a cellular migration from the lobules to early septa.