A placental lesion, characterized by fibrinoid and trophoblastic necrosis with massive infiltration of the intervillous space by mononuclear cells (massive chronic intervillositis, MCI), was observed in six cases, five with intrauterine growth retardation (IUGR) and one with sudden intrauterine fetal death. Four out of six had chronic villitis of unknown etiology (CVUE) associated with this lesion, and five had lesions of anchoring villitis. In three cases, acute atherosislike lesions in spiral arteries of parietal and/or basal decidua were observed. Massive deposits of IgM, a smaller amount of C3 and Clq, and slight deposits of IgG and IgA were found in these vessels. Neither mothers nor infants had any clinical or serological evidence of infection. Cases with MCI were compared with those having CVUE without intervillositis. Patients with MCI showed lower values of infant weight, infant length, and ponderal index than controls. However, cases with MCI group showed a higher incidence of IUGR. Placentas from the MCI group had a greater number of acute atherosislike lesions than controls. Massive chronic intervillositis may represent an extreme variant of villitis of unknown etiology. A maternal immunological aggression toward fetal tissues is proposed as pathophysiological mechanism, although a nondetermined placental infection cannot be excluded.

In January 2015, a 20-month-old child and her family took part in recreational activities at Carrasco and Malvín beaches (Montevideo, Uruguay). An intense harmful algae bloom (HAB) was developing along the coast at that time. A few hours after the last recreational exposure episode, the family suffered gastrointestinal symptoms which were self-limited except in the child’s case, who was admitted to hospital in Uruguay with diarrhea, vomiting, fatigue, and jaundice. The patient had increased serum levels of liver enzymes and bilirubin and five days later presented acute liver failure. She was referred to the Italian Hospital in Buenos Aires, being admitted with grade II–III encephalopathy and hepatomegaly and requiring mechanical respiratory assistance. Serology tests for hepatitis A, B, and C, Epstein-Barr virus, and cytomegalovirus were negative. Laboratory features showed anemia, coagulopathy, and increased serum levels of ammonium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Autoimmune Hepatitis Type-II (AH-II) was the initial diagnosis based on a liver kidney microsomal type 1 antibodies (LKM-1) positive result, and twenty days later a liver transplant was performed. The liver histopathology had indicated hemorrhagic necrosis in zone 3, and cholestasis and nodular regeneration, which were not characteristic of AH-II. LC/ESI-HRMS (liquid chromatography electrospray ionization high-resolution mass spectrometry) analysis of MCs in the explanted liver revealed the presence of Microsytin-LR (MC-LR) (2.4 ng·gr−1 tissue) and [D-Leu1]MC-LR (75.4 ng·gr−1 tissue), which constitute a toxicological nexus and indicate a preponderant role of microcystins in the development of fulminant hepatitis.

Background/AimsLiver biopsy represents the gold standard for damage evaluation, but noninvasive serum markers that mirror liver fibrosis progression are actual goals both in adults and especially in children. The aim was to determine specific serum markers that correlate with liver fibrosis progression during chronic HCV infection.MethodsLiver biopsies and concomitant serum samples from 22 pediatric and 22 adult HCV patients were analyzed. Histological parameters were evaluated. On serum TGF-ß1, tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1), hyaluronic acid (HA) and aminoterminal peptide of procollagen type III (PIIINP) were tested.ResultsSignificant fibrosis (F≥2) and advanced fibrosis (F≥3) represented 64% and 20%, respectively in children; while 54% F≥2 and 23% F≥3 in adults. Hyaluronic acid (p = 0.011) and PIIINP (p = 0.016) were related to worse fibrosis stages only in adults, along with TIMP-1 (p = 0.039) just in children; but TGF-ß1 was associated with mild fibrosis (p = 0.022) in adults. The AUROC of TIMP-1 in children to discriminate advanced fibrosis was 0.800 (95%IC 0.598–0.932). In adults, the best AUROCs were that of HA, PIIINP and TGF-ß1 [0.929 (IC95% 0.736–0.994), 0.894 (IC95% 0.689–0.984) and 0.835 (IC95% 0.617–0.957)], respectively. In children, according to the cut off (165.7 ng/mL) value for TIMP-1, biopsies could have been avoided in 72% (18/25). Considering the cut off for HA (109.7 ng/mL), PIIINP (9.1 µg/L), and TGF-ß1 (10,848.3 pg/mL), biopsies could have been avoided in 87% (19/22) of adult patients by using HA and 73% (16/22) using PIIINP or TGF-ß1.ConclusionsIn adults given the diagnostic accuracy of HA, PIIINP, TGF-ß1, their combination may provide a potential useful tool to assess liver fibrosis. This first pediatric study suggests that TIMP-1 is clinically useful for predicting liver fibrosis in HCV patients.

We have investigated the presence and clinical implications of maternal vascular lesions and chronic villitis of unknown etiology (CVUE) in 18 placentas of 15 mothers with several autoimmune diseases (AD), including, for the first time, idiopathic thrombocytopenic purpura, autoimmune thyroid diseases, and multiple sclerosis. The group with AD had significantly more maternal vascular lesions and CVUE than the control group. We did not find lesions that could be attributed to any of the diseases in particular. The histopathologic picture was similar in these diseases, although there appears to be a spectrum in severity. Placental vascular damage with deposits of IgM, C3, and C1q was more prominent in systemic lupus erythematosus and in a patient with systemic sclerosis. In both of these diseases but not in the other conditions, these lesions were related to poor fetal outcome. Although the precise role of each of these autoimmune diseases in pregnancy and fetal outcome remains to be established, there appears to be at least one link between them represented by the presence of severe acute atherosis and heavy granular vascular deposits of IgM, C3, and C1q associated in some with poor fetal outcome. The role of CVUE remains speculative.

The recategorization of former N3 involved a high proportion of positive node cases. Current N1/N2 categories clearly defined different outcomes and were not modified by the integration of former N3.