ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Drug-induced liver injury (DILI) is a leading cause of acute liver failure in developed countries. Hepatotoxicity is a well-recognized adverse effect associated with synthetic oestrogens, which can cause cholestasis. The current report describes ethinyloestradiol (EE2)-associated highly unusual adverse effects of autoimmune hepatitis (AIH) and microvesicular steatosis (MS). DILI that fulfils the criteria for AIH is referred to as drug-induced autoimmune hepatitis (DIAIH). MS is a potentially severe liver lesion that results from mitochondrial dysfunction. We explore the pathophysiological mechanisms underlying DIAIH and MS. CASE SUMMARY: A 51-year-old woman presented with jaundice, increased liver enzymes and IgG, and positive ANA. She had been taking EE2 for 3 years. Liver biopsy showed prominent interface hepatitis with MS. A drug-lymphocyte stimulation test (DLST) using EE2 was positive. The liver biochemical parameters had normalized after the EE2 discontinuation; however, they exacerbated 5 months post-onset. Repeated liver biopsy showed interface hepatitis with no MS. Considering EE2-induced DIAIH, corticosteroids treatment was initiated. Then, all liver biochemical parameters had normalized, and the corticosteroids were successfully withdrawn. The patient continued to be in complete remission over the next 3 years. WHAT IS NEW AND CONCLUSION: Five remarkable points should be emphasized: (i) a long latency interval, despite the acute presentation; (ii) exacerbation of liver biochemical parameters, even after drug cessation; (iii) the paired liver biopsies indicating continuing inflammation and disappearance of toxic features; (iv) a positive DLST and the absence of fibrosis consistent with DIAIH and not AIH; and (v) a rare histological feature of MS. Intense immunoallergic reactions were likely triggers of MS in the current case. A possibility of DIAIH should be considered in cases of DILI which exhibit overt jaundice, autoantibodies, intense histological inflammation and a long latency period.
Subject(s)
Chemical and Drug Induced Liver Injury/diagnosis , Ethinyl Estradiol/adverse effects , Fatty Liver/diagnosis , Hepatitis, Autoimmune/diagnosis , Chemical and Drug Induced Liver Injury/blood , Diagnosis, Differential , Fatty Liver/blood , Fatty Liver/chemically induced , Female , Hepatitis, Autoimmune/blood , Humans , Middle AgedABSTRACT
Passive immunisations with a monoclonal antibody termed 1-5H showed a partial but significant inhibition of parasitaemia against Babesia microti challenge infection. By immunoscreening with 1-5H, a clone (termed p58 gene) was obtained from a cDNA expression library of B. microti and the complete nucleotide sequence was determined. A protein homology search showed significant amino acid identities to the eta subunit of the chaperonin containing T-complex protein 1 (CCT) of human (59%), mouse (58%) and Plasmodium falciparum (62%). Genomic analyses indicated that the p58 gene is present as a single copy gene and contains a total of approximately 400-bp introns in the genome of B. microti. The mAb 1-5H recognised a 58-kDa protein of B. microti and was found to cross-react with a 60-kDa protein of Babesia rodhaini. These results suggest the possibility that the p58 protein is the CCT eta subunit of B. microti and functions as a chaperonin.
Subject(s)
Antigens, Protozoan/genetics , Babesia/genetics , Chaperonins/genetics , Amino Acid Sequence , Animals , Antibodies, Monoclonal/biosynthesis , Antibodies, Monoclonal/immunology , Antigens, Protozoan/immunology , Babesia/immunology , Babesiosis/immunology , Babesiosis/therapy , Base Sequence , Chaperonin Containing TCP-1 , Chaperonins/immunology , Electrophoresis, Polyacrylamide Gel , Female , Fluorescent Antibody Technique, Indirect , Gene Library , Immunization, Passive , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Parasitemia/immunology , Parasitemia/therapy , Polymerase Chain Reaction , Sequence Homology, Amino AcidABSTRACT
We retrospectively reviewed 32 patients who underwent parathyroidectomy at our hospital for the last fourteen years. 1) Clinical appearance of primary hyperparathyroidism was in younger age in women. 2) In previous history or at the time of PTX, 9 patients had malignant tumors including 6 thyroid cancers, 36% of the patients with out bone related symptoms had a remarkable decrease in bone mineral content. 3) After PTX, none of patients had recurrent urolithiasis and bone mineral content of all patients was significantly increased in a short time. In addition, upper GI complaints were improved, or hypertension was partially normalized. However, renal insufficiency remained unchanged. 4) In preoperative localization study, Ultrasound sonography (US) demonstrated the best accuracy rate of 88% when only one gland was involved. US was able to detect multiple gland involvement only in 20% of 5 cases. 5) Hypercalciuria was recognized as one of the risk factors of stone formation in patients with primary hyperparathyroidism.
