Delia M. Paternoster

Hepatitis C virus infection in pregnancy

Objective To evaluate the clinical aspects of hepatitis C virus (HCV) liver disease in anti‐HCV + ve mothers, both during pregnancy and six months after delivery, and to assess the outcome of pregnancy.

Intra-hepatic cholestasis of pregnancy in hepatitis C virus infection.

Background. Aims of this study were to investigate whether hepatitis C virus infection influences the incidence and natural history of intrahepatic cholestasis of pregnancy (ICP) and whether ICP has different characteristics in hepatitis C virus (HCV) positive women from ICP in HCV negative women.

S-adenosylmethionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial

OBJECTIVES To evaluate the efficacy of S-adenosylmethionine (SAMe) and ursodeoxycholic acid (UDCA) in intrahepatic cholestasis of pregnancy (ICP). METHODS Twenty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (1000 mg/day i.m.) or UDCA (450 mg/day) until delivery; the treatment lasted at least 15 days in all cases. RESULTS After UDCA the women exhibited significantly lower levels of total bile acids (P < 0.02), but no significant differences were noted in AST, ALT, or alkaline phosphatase. All ten patients showed a complete resolution of pruritus. After SAMe no significant changes were noted in pruritus, total bile acids or liver function tests. No adverse reactions on mother or child were recorded during either UDCA or SAMe treatment and the outcome of pregnancy was favorable in both groups. CONCLUSIONS These findings show that UDCA is more effective than SAMe in controlling pruritus and total bile acids, which are considered a prognostic parameter in ICP with respect to the fetus. Nevertheless, before UDCA is introduced as an effective and safe treatment for ICP, which also has a beneficial effect on fetal prognosis, we believe these results should be confirmed and extended in other clinical trials.

Viral load in HCV RNA-positive pregnant women

Abstract OBJECTIVES: The risk of hepatitis C virus (HCV) infection in the newborn is estimated to be around 5%, but becomes very high in the case of coinfection with HIV. One of the main factors associated with the vertical transmission of HCV is the viral load. Our objective was to investigate the behavior of HCV viral load during pregnancy in relation to HIV coinfection, liver enzymes, and vertical transmission. METHODS: Three thousand seven hundred forty-eight women seen consecutively in their first trimester of pregnancy were screened for HCV infection. Sixty-five were found to be anti-HCV+/HCV RNA+ and were followed up with clinical and serological assessment ( i.e., transaminases and quantitative polymerase chain reaction [PCR] for viral load) in their second and third trimesters and 6 months after delivery. All were anti-HIV and hepatitis B surface antigen negative. HCV RNA was 12.0 ± 19.9 × 10 6 copies/ml in the first trimester and 10.9 ± 13.3 × 10 6 in the second, but increased to 19.5 ± 25.1 × 10 6 in the third trimester. Six months after delivery the viral load returned to the baseline levels; the changes in viral load did not reach any statistical significance, however. Transaminases tended toward a reduction from the baseline during the second and third trimesters, and then an increase in both AST and ALT was recorded 6 months after delivery. However, when the group whose AST/ALT were found abnormal at the first test was considered, no significant changes were recorded during the follow-up. The overall rate of vertical transmission was 4.6%. CONCLUSIONS: With HCV+ mothers monitoring transaminases during pregnancy is unnecessary, and testing liver enzymes at the beginning of pregnancy is sufficient. Qualitative PCR should be done once during the pregnancy, but any staging of the liver disease should be taken after delivery. Quantitative PCR testing is expensive and pointless. Any decision for elective cesarean section in HCV RNA+ mothers should be confirmed by other studies.

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy

A. F L O R E A N I Senior Registrar (Gastroenterology), *D. P A T E R N O S T E R Senior Registrar (Obstetrics & Gynaecology), * V. GRELLA Professor (Obstetrics & Gynaecology), * S . S ACCO Research Fellow (Obstetrics), * M. GANGEMI, Associate Professor (Obstetrics), M. CHIARAMONTE Associate Professor (Gastroenterology) Department of Gastroenterology. Institute of Internal Medicine & * Institute of Gynaecology and Obstetrics, University of Padova, Italy

C-reactive protein in hypertensive disorders in pregnancy

Hypertension is the most frequent medical complication of pregnancy. A recent report demonstrates the flogistic pathogenesis of pregnancy-induced hypertension. Because C-reactive protein (CRP) is a marker of inflammation, it can be used in the differential diagnosis of hypertensive disorders of pregnancy. A total of 322 pregnant women at 24 to 32 weeks’ gestation were enrolled. The control group (A) comprised 190 women. Sixty-three women had preeclampsia (PE, group B), 31 women presented transient hypertension (TH, group C), 19 had HELLP syndrome (HS, group D) and 19 had chronic hypertension (CH, group E). CRP serum concentrations were significantly higher in groups B, C, and D in comparison with the group A. In the whole population, systolic and diastolic pressure value inversely correlate with weight at delivery and weeks of gestation at delivery. CPR levels in patients with PE and HS inversely correlate with birth weight and gestational week at delivery. Normal plasma levels of CRP may be an important marker of differential diagnosis between TH and CH. In TH, PE, and HS, CRP levels were higher than in the control and CH groups, suggesting that inflammation may be the common pathogenetic cause of TH and PE. Finally CRP levels in preeclampsia are believed to correlate with preeclamptic process severity.

Cervical phIGFBP-1 in the evaluation of the risk of preterm delivery

Background. To evaluate the accuracy of the decidual phosphorylated isoform of insulin‐like growth factor binding protein‐1 in endocervical secretions to predict premature delivery in symptomatic and asymptomatic pregnant women. Methods. The study included 332 pregnant women: 109 symptomatic patients (study group) and 223 asymptomatic women (control group). For all women, qualitative and quantitative assessment of the decidual phosphorylated isoform of insulin‐like growth factor binding protein‐1 in endocervical secretions was carried out, but the quantitative assay was finally performed in 282 of 332. Students test, the φ2 test, and Fishers exact test were used as appropriate. Results. The phosphorylated insulin‐like growth factor binding protein‐1 qualitative test was positive in 35 of 301 women (11.6%) and 11 (31.4%) of them delivered before 37 weeks; in the remaining 266 women with a negative test, there were 11 (4.7%) premature deliveries (relative risk=5.8; 95% CI=3.3–10.3). The mean values of quantitative phosphorylated isoform of insulin‐like growth factor binding protein‐1 were 56.9 µg/l (95% CI=40.7–73.1) in cases of a positive qualitative test and 6.1 µg/l (95% CI=4.0–8.3; p = 0.0001) in women with a negative result. The sensitivity, specificity, positive predictive value, and negative predictive value for phosphorylated isoform of insulin‐like growth factor binding protein‐1 test in symptomatic patients were 69.2%, 90.5%, 50%, and 95.6% respectively, while in the asymptomatic patients they were 22.2%, 91.8%, 11.8%, and 96% respectively. Conclusions. The phosphorylated isoform of insulin‐like growth factor binding protein‐1 in cervical secretions is a potential specific marker for preterm delivery occurring before 37 weeks. This test may have an important role in the management of women presenting with symptoms suggestive of preterm labour.

Hepatitis C virus, hepatitis B virus and human immunodeficiency virus infection in pregnant women in North-East Italy: A seroepidemiological study

Background: Pregnant women can be considered a sentinel population, because they are a relatively unselected population whose prevalence data may be extended to the general population. Methods: A seroepidemiological study was carried out in Padua (North-East Italy) to assess the epidemiological aspects of HCV, HBV and HIV infection in 2059 pregnant women consecutively seen at the Department of Obstetrics and Gynaecology during 1996. Out of them, 1804 (87.2%) were indigenous and 255 (12.8%) immigrants. Sociodemographical and sanitary data were collected for each woman. Results: The overall prevalence of anti-HCV was 1.9% (42.5% with detectable HCV-RNA); HBsAg was found in 1.0%; the prevalence of anti-HIV was 0.3%. Findings are substantially consistent with the epidemiological picture of such infections in the general population of our geographic area. A parenteral risk factor for HCV infection was found in 19 subjects (47.5%): 18 were intravenous drug users and 1 a blood transfusion recipient. HBsAg seroprevalence was higher in immigrants than in autochthonous (3.1% vs. 0.7% respectively, p < 0.01). One of the 6 anti-HIV positive women was intravenous drug user. Logistic regression analysis was carried out for each viral agent to determine which characteristics were independently associated with infection: anti-HCV prevalence resulted independently associated to Italian origin (OR: 3.7), unmarried status (OR: 2.7), unemployed condition (OR: 6.1) and history of previous abortion (OR: 2.8). HBsAg prevalence was independently associated to unemployed condition (OR: 10.8), whereas HIV positivity was significantly related to the unmarried status (OR: 18.5). Conclusion: Our study pinpoints the need of screening all pregnant women for HCV and HIV infection, in addition to the HBsAg screening which is compulsory in Italy.

The contraceptive vaginal ring in women with renal and liver transplantation: analysis of preliminary results.

INTRODUCTION Vaginal administration seems to be the best route to achieve steady and precise doses of contraceptive hormones, resulting in stable serum concentrations and low exposure. The aim of this study was to evaluate the contraceptive efficacy, cycle control, tolerability and acceptability of a contraceptive vaginal ring (NuvaRing) in renal and liver transplant recipients. MATERIAL AND METHODS Renal or liver transplant recipients, asking for contraception, were enrolled into the study. The duration of treatment was 12 cycles, with each vaginal ring releasing an average of 120 mg etonogestrel and 15 mg ethinylestradiol daily. Study visits were scheduled at screening, in the first week following cycles 3, 6, and 12 (172 cycles). RESULTS Among 17 females included into the study: were 9 renal (mean age, 30 +/- 7.2 years) and 8 liver transplant recipients (mean age, 32.6 +/- 6.6 years). At the onset of therapy all patients showed at least 6 months of stable graft function with no signs of allograft rejection. The mean posttransplant follow-up was 4 +/- 3.6 and 5.3 +/- 2.1 years for women with renal and hepatic transplantations respectively (P = NS). The immunosuppressive therapy was not changed for any patient. We demonstrated good cycle control: 162 cycles did not exhibit any bleeding; 7 cycles, only spotting episodes, whereas 2 cycles had 1 bleeding episode during the ring period. The estrogen-related adverse events (nausea and breast tenderness) were reported in 2 patients. One patient experienced significant bleeding related to thrombocytopenia. DISCUSSION Nuvaring, in our preliminary findings, may be considered to be an highly effective contraceptive method for female transplant recipients that additionally regulate menstrual bleeding and seems to positively influence well-being. Vaginal administration may diminish the chance of drug interactions and therefore be safer for patients.

Sex hormone profile and endometrial cancer risk in primary biliary cirrhosis: a case-control study.

OBJECTIVE To investigate the sex hormone profile and endometrial histology in primary biliary cirrhosis (PBC). STUDY DESIGN A prospective case-control study. Twenty-two females with PBC and 22 sex- and age-matched healthy controls underwent complete gynaecological examination including endometrial biopsy and a sex hormone serological profile including: oestrone, 17-beta oestradiol, testosterone, progesterone, dehydroepiandrosterone sulphate (DHEA-S) and sex hormone binding protein (SHBG). The sex hormone profile was evaluated with respect to the body mass index (BMI), anthropometric measurements and endometrial histological/cytological patterns in each case. Statistical analysis was done with the chi-squared method, Students t-test for unpaired data, linear regression analysis, Spearmans rank correlation test and stepwise multiple regression analysis. RESULTS The BMI was comparable in the two groups, while PBC cases had significantly smaller subscapular, waist, bicipital, tricipital and calf fold measurements than controls. Testosterone serum levels were significantly lower in PBC cases than in controls (0.9+/-0.6 versus 1.4+/-0.7 mmol/l, P<0.03), whereas SHBG was significantly higher than in controls (88.6+/-72.1 versus 63.6+/-27.6, P<0.005). No significant differences between the two groups were found for oestrone, 17-beta oestradiol, DHEA-S, and progesterone levels. No difference patterns were observed in endometrial histological/cytological patterns. Multiple regression analysis identified SHBG as an independent variable associated with PBC. CONCLUSIONS Changes in sex hormone profile are secondary to hepatic dysfunction in PBC. Females with PBC do not appear to carry a higher risk of endometrial cancer.