Factors influencing outcome of lamivudine in anti-HBe-positive chronic hepatitis B

BACKGROUND/AIMS: Lamivudine has been shown to benefit patients with anti-HBe/HBV-DNA-positive chronic hepatitis B. The aim of the study was to evaluate factors influencing outcome of lamivudine therapy during two years of post-treatment follow-up in a prospective clinical trial. METHODOLOGY: Thirty-one consecutive patients, submitted to liver biopsy, were treated with lamivudine at 100mg/daily for twelve months and followed-up for twenty-four months. The patients were never treated before with interferon or stopped at least six months before starting lamivudine. ALT was measured monthly and HBV-DNA every three months. RESULTS: At the end of therapy 25 (81%) patients had both biochemical and virological response; 2 (6%) patients showed persistent viremia and 4 (13%) patients developed viral resistance during treatment. Twenty-three (92%) out of 25 responders relapsed during the follow-up; over 50% of all cases relapsed within 6 months. The relapse is related to higher HBV-DNA baseline levels. At relapse, 4/23 (17%) patients had symptomatic acute hepatitis. CONCLUSIONS: Lamivudine is associated with the risk of developing viral mutants and, after therapy discontinuation, to high rate of relapse. In relapsing patients severe acute recurrence of hepatitis B may occur. Decisions about lamivudine monotherapy should take into account the limited long-term efficacy, effects of relapse, costs and predictive factors for response.     

Human papilloma virus (HPV) status, p16INK4a, and p53 overexpression in epithelial malignant and borderline ovarian neoplasms

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16(INK4a), and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer.     

Incidental finding of mammary carcinoma in lumpectomy specimens

More and more breast lumpectomies are being performed due to mammographic screening, and both in situ and invasive breast carcinomas are being detected earlier and smaller in size. The objective of this study was to determine the presence of incidental microscopic breast carcinoma in mammography-guided lumpectomy specimens. A prospective study was carried out by processing in surgical pathology approximately 9,000 breast lumpectomy specimens during a 2.5-yr period so that the entire specimens were embedded for microscopic examination. Excluded from the study were cases with grossly or microscopically identified carcinomas greater than 10 mm2, and non-invasive carcinomas diagnosed in association with invasive carcinoma. Cases with multifocal carcinomas, prior diagnosis of breast cancer, or prior history of breast biopsy were also excluded. Carcinomas present in the same tissue blocks as the clinically suspected lesions such as palpable nodules, microcalcification, or other mammographic abnormalities were excluded as well. Fifty cases of incidental microscopic mammary carcinoma were found including 8 infiltrating ductal carcinomas (IDC), 2 infiltrating lobular carcinomas (ILC), 21 intraductal carcinomas (DCIS), and 19 lobular carcinomas in situ (LCIS). All of the lesions were solitary, located in indistinct loosely arranged fibrous and adipose stromal tissues, and the majority of them were near or at the inked excisional margins. Physicians who care for patients with breast cancer should be aware of the existence of these minute breast carcinomas that are often near or at the surgical margins. The significance of these microscopic findings for therapeutic strategy and prognosis should be determined by long-term follow-up.     

Autoimmune thyroid disease and celiac disease in children

BACKGROUND: Celiac disease (CD) may be associated with other immunologic disorders in adults and children. Previous studies linking CD and autoimmune thyroid disease in children have included very few patients with limited biochemical and immunologic screening tests. The aim of this multicenter study was to establish the prevalence of autoimmune thyroid involvement in a large series of pediatric patients with CD. METHODS: Five hundred seventy-three consecutive pediatric patients were enrolled from clinics in Torino, Bologna, Foggia, Rome (two clinics), Naples, and Bari. Three hundred forty-three patients with CD were studied, 230 girls and 113 boys (median age, 8.5 years). Two hundred fifty-six of the patients with CD (median age, 9 years) had been following a gluten-free diet for 3 months to 16 years; 87 patients were untreated (median age, 6.2 years). The diagnosis of CD was made using the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. A control group of 230 subjects (median age, 8.3 years) was enrolled. Serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone (TSH), antithyroperoxidase, antithyroglobulin, anti-TSH receptor antibodies, and thyroid echographic pattern were considered. RESULTS: Autoimmune thyroid disease was found in 90 of 343 (26.2%) patients with CD (62 on a gluten-free diet) and in 20 (10%) of the control subjects (P = 0.001). Fifty-four (15.7%) patients with CD and autoimmune markers had normal thyroid function (euthyroidism) as did 12 (6.0%) of the control subjects; hypothyroidism was observed in 28 (8.1%) patients with CD and in 7 (3.5%) of the control subjects. Hyperthyroidism was diagnosed in four patients with CD and in none of the control subjects with autoimmune markers. An abnormal echographic pattern was seen in 37 patients with CD (16.8%) and only in 1 (1.6%) of the control subjects (P = 0.002). CONCLUSIONS: The high frequency of autoimmune thyroid disease found among patients with CD, even those on a gluten-free diet, may justify a thyroid status assessment at diagnosis and at follow-up evaluation of children with CD.     

Congenital cytomegalovirus infection in twin pregnancies: viral load in the amniotic fluid and pregnancy outcome

Human cytomegalovirus (CMV) is the most common cause of viral intrauterine infection and fetal damage largely attributable to maternal primary infection. Most cases of congenital CMV infection in twins reported in the literature involved only 1 twin. We assessed the validity of polymerase chain reaction (PCR) and quantitative PCR on amniotic fluid (AF), at 21 to 22 weeks' gestation and at least 6 to 8 weeks after seroconversion, to predict the outcome of newborns in twin pregnancies. Two pregnant women with twin pregnancies and 1 woman with a triple pregnancy with primary CMV infection defined by the presence of immunoglobulin (Ig) M and low IgG avidity and/or by the presence of clinical symptoms and abnormal liver enzyme values were evaluated. CMV infection was found in 6 fetuses/newborns, 3 of whom were symptomatic. In the first twin pregnancy with diamniotic-dichorionic separate placentas, CMV symptomatic infection of the female twin was demonstrated by positive virus isolation and high viral load in AF. The male fetus was not infected as demonstrated by negative CMV culture and DNA detection in AF. In the triple pregnancy, the woman had a placenta with 2 monozygotic twins (females) and a separate placenta with a heterozygotic twin (male). The quantitative PCR results were 10(3) genome equivalents (GE)/mL of females AF and 1.9 x 10(5) GE/mL of male AF. Both female twins were asymptomatic at birth, whereas the male presented petechiae, thrombocytopenia, and cerebral ventriculomegaly. In the last twin pregnancy with fused dichorionic placentas, congenital CMV infection of both twins was diagnosed at birth in contrast with prenatal diagnosis. At time of amniocentesis, the left side twin was not infected as shown by negative results of CMV culture and DNA detection in the AF. CMV infection of the right side twin was demonstrated by positive CMV DNA detection with a CMV DNA load of 4.9 x 10(4) GE/mL and positive virus isolation in the AF. The morphologic and histologic examinations of the placentas strongly supported a prenatal horizontal acquisition of CMV infection. These twin pregnancies showed a marked difference in the quantity of virus load documented by the prenatal diagnosis suggesting that twin fetuses may react differently to primary maternal infection despite being exposed to the same maternal influences. A high viral load is correlated with congenital CMV infections symptomatic at birth. In such cases, with fetal infection of only 1 twin (at amniocentesis) and fusion of placentas, fetal outcome of both twins needs to be evaluated for the possibility of viral transfer from one fetus to the other.     

Successful tenofovir treatment for fulminant hepatitis B infection in an infant

Fulminant hepatic failure is defined by the presence of severe impairment of liver function, with or without encephalopathy, in patients with no underlying chronic liver disease. We report the case of a 4-month-old infant who developed fulminant hepatitis B infection and recovered concomitant with tenofovir therapy without liver transplantation.     

Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study

BACKGROUND: Infertile women positive for thyroid antibodies suffer from a poor pregnancy/delivery outcome, although conflicting data have been published. Our objective was to investigate if levothyroxine (LT4) exerts any effect on pregnancy and/or delivery rates in thyroid peroxidase antibody (TPOAb)-positive (+) women undergoing assisted reproductive technologies. METHODS: Patients undergoing treatment were screened for TPOAb, thyroid-stimulating hormone (TSH) and free thyroxine (FT4). A total of 72 (15%) out of the 484 euthyroid women selected were TPOAb (+). These 72 patients were randomly divided into two groups: group A (n = 36) underwent LT4 treatment, group B (n = 36) placebo. Group C consisted of 412 women (85%) who were TPOAb negative (-). All patients received controlled ovarian stimulation. The endpoints of treatment were pregnancy rate, miscarriage rate and delivery rate. RESULTS: No differences in pregnancy rate were observed between the three groups. Miscarriage rate was higher in TPOAb (+) in comparison to TPOAb (-) [relative risk: 2.01 (95% CI = 1.13-3.56), P = 0.028]. CONCLUSIONS: The pregnancy rate is not affected either by presence of TPOAb or treatment with LT4. However, TPOAb (+) women show a poorer delivery rate compared to TPOAb (-). LT4 treatment in TPOAb (+) does not affect the delivery rate.