Background Recent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical and genetic features of 108 subjects. Methods Between Sep 2010—Dec 2012, 108 subjects with acute porphyrias [90 acute intermittent porphyria, 9 hereditary coproporphyria, 9 variegate porphyria] were enrolled into an observational study. Genetic testing was performed at a central genetic testing laboratory and clinical information entered into a central data base. Selected features were compared to data for adults in the USA. Results Most subjects [88/108, 81%] were female with self-reported onset of symptoms in 2nd–4th decades of life. The most common symptom was abdominal pain. Appendectomies and cholecystectomies were common prior to a diagnosis of porphyria. The diagnosis was delayed by a mean of 15 years. Anxiety and depression were common, and 18% complained of chronic symptoms, especially neuropathic and other pains. The incidences of and systemic arterial hypertension, chronic kidney disease, seizure disorders, and psychiatric conditions were markedly increased. Mutations of the known causative genes were found in 102/105 of those tested, with novel mutations being found in 37 including in 7/8 subjects with hereditary coproporphyria. Therapy with intravenous hematin was the most effective therapy both for treatment of acute attacks and for prevention of recurrent attacks. Conclusions Acute porphyrias often remain undiagnosed for more than a decade after first symptoms develop. Intravenous hematin is the treatment of choice, both for treatment of acute attacks and for prevention of recurrent attacks. Trial Registration clinicaltrials.gov identifier: NCT01561157

+ T cells and macrophages. DILI cases had significantly fewer B lymphocytes than AIH and VH and significantly fewer NK cells than VH. Prominent plasma cells were unusual in IAD (three of 10 cases), but were associated strongly with AIH (eight of nine) and also observed in most with AID (six of nine). They were also found in five of 10 cases with VH. Liver biopsies from subjects with DILI were characterized by low counts of mature B cells and NK cells in portal triads in contrast to VH. NK cells were found only in cases of VH, whereas AIH and VH both showed higher counts of B cells than DILI. Plasma cells were associated most strongly with AIH and less so with AID, but were uncommon in IAD.

Blockade of various immune targets such as cytotoxic T-lymphocyte antigen-4 and Programmed cell death leads to immune-mediated tumor regression and immune-related adverse events, predominantly gastrointestinal events including diarrhea and colitis. The current review is done to understand the underlying mechanism of action and to identify potential biomarkers that could help in the prediction and management of gastrointestinal immune-related adverse events. Histological assessment of bowel biopsies and assessment of serologic markers of inflammatory bowel disease and colitis secondary to immune mediated antibodies are reviewed. Ipilimumab causes dysregulation of gastrointestinal mucosal immunity, which can be evidenced by altered antibody levels to enteric flora and inflammatory cell infiltration into gastrointestinal mucosa associated with diarrhea and clinical evidence of colitis. The pattern of drug induced antibody titers to microbial flora and the histological features and location of the inflammation were distinct from classic inflammatory bowel disease. Although classic inflammatory bowel disease and immune mediated antibodies related gastrointestinal toxicity are both immune mediated, the pattern of biomarkers and histological features suggests that the later may be a distinct clinicopathologic entity.

Acute liver failure (ALF) during pregnancy is very uncommon. Pregnancy-specific liver conditions like hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and acute fatty liver of pregnancy can cause ALF at term or postpartum, but, typically occur during the third trimester. Most of these patients recover spontaneously after delivery, but, on occasion, they require liver transplantation in the postpartum period. However, ALF during the first and second trimester of pregnancy requiring antepartum liver transplantation is rare. Only fifteen cases of liver transplantation during pregnancy have been reported, and very few occurred during the first trimester. We report a Woman who developed acute liver failure during the first trimester of pregnancy and underwent successful liver transplantation at 11-week gestation, followed by successful delivery of the fetus at 30 weeks. To our knowledge, this is the earliest case of successful liver transplantation during pregnancy followed by successful fetal outcome. We discuss management of the patient and fetus before, during, and after liver transplantation and review the literature on antepartum liver transplant in pregnancy.

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