Early diagnosis of bacterial and fungal infection in chronic cholestatic hepatitis B.
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AIM: To investigate the early diagnostic methods of bacterial and fungal infection in patients with chronic cholestatic hepatitis B. METHODS: One hundred and one adult in-patients with chronic hepatitis B were studied and divided into 3 groups: direct bilirubin (DBil)/total bilirubin (TBil) > or = 0.5, without bacterial and fungal infection (group A, n=38); DBil/TBil <0.5, without bacterial and fungal infection (group B, n=23); DBil/TBil> or = 0.5, with bacterial or fungal infection (group C, n=40). The serum biochemical index and pulse rate were analyzed. RESULTS: Level of TBil, DBil, alkaline phosphatase (ALP) and DBil/ALP in group A increased compared with that in group B. The level of ALP in group C decreased compared with that in group A, whereas the level of TBil, DBil and DBil/ALP increased (ALP: 156+/-43, 199+/-68, respectively, P<0.05; TBil: 370+/-227, 220+/-206, respectively, P<0.01; DBil: 214+/-143, 146+/-136, respectively, P<0.01; DBil/ALP: 1.65+/-1.05, 0.78+/-0.70, respectively, P<0.001). The level of DBil and infection affected DBil/ALP. Independent of the effect of DBil, infection caused DBil/ALP to rise (P<0.05). The pulse rate in group A decreased compared with that in group B (63.7+/-6.4, 77.7+/-11.4, respectively, P<0.001), and the pulse rate in group C increased compared with that in group A (81.2+/-12.2, 63.7+/-6.4, respectively, P<0.001). The equation (infection=0.218 pusle rate +1.064 DBil/ALP -16.361), with total accuracy of 85.5%, was obtained from stepwise logistic regression. Pulse rate (> or =80/min) and DBil/ALP (> or =1.0) were used to screen infection. The sensitivity was 62.5% and 64.7% respectively, and the specificity was 100% and 82.8% respectively. CONCLUSION: Bacterial and fungal infection deteriorate jaundice and increase pulse rate, decrease serum ALP and increase DBil/ALP. Pulse rate, DBil/ALP and the equation (infection=0.218 pusle rate+1.064 DBil/ALP-16.361) are helpful to early diagnosis of bacterial and fungal infection in patients with chronic cholestatic hepatitis B. (+info)
Hydrochlorothiazide and other thiazide-like diuretics are considered as a first-line drug for initial therapy in uncomplicated arterial hypertension [1]. There are several reports [2-6] of thiazide-induced cholecystitis, but here we report a case of serious hepatotoxicity associated with hydrochlorothiazide treatment. (+info)
Reduced hepatic expression of farnesoid X receptor in hereditary cholestasis associated to mutation in ATP8B1.
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Farnesoid X receptor (FXR) is a transcription factor that controls bile acid homeostasis. The phenotype of Fxr null mice is characterized by hypercholanaemia, impaired secretion of bile acids and failure to thrive. Human disorders with these characteristics include FIC1 disease (caused by mutations in ATP8B1, which encodes a putative aminophospholipid translocase, FIC1, whose function in bile handling is unknown) and bile salt export pump (BSEP) disease (caused by mutation in ABCB11, which encodes BSEP, the primary canalicular bile salt export pump). We investigated the possibility of hepatic down-regulation of FXR in FIC1 disease and BSEP disease. Three siblings with this phenotype, born to consanguine parents, were initially studied. The children were demonstrated to be compound heterozygotes for missense and nonsense mutations in ATP8B1. Expression of specific genes in liver was analysed, comparing one of these siblings with a child homozygous for missense mutation in ABCB11, as well as with a child having idiopathic cholestatic liver disease, a child with extrahepatic biliary atresia and a normal organ donor. The expression of two main FXR isoforms was specifically decreased in the liver of the FIC1 disease patient. A consistent and concomitant reduction in messenger RNA levels of FXR targets, such as BSEP and small heterodimer partner, was also found. Gene-profiling experiments identified 163 transcripts whose expression changed significantly in FIC1-disease liver. Of note was that several genes involved in synthesis, conjugation and transport of bile acids were down-regulated. A cluster of genes involved in lipid metabolism was also differentially expressed. Our findings suggest that hepatic down-regulation of FXR contributes to the severe cholestasis of FIC1 disease. (+info)
Sequence variation in the ATP8B1 gene and intrahepatic cholestasis of pregnancy.
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Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic condition that may affect women during the third trimester of pregnancy. Symptoms experienced by these women generally resolve spontaneously following delivery, but prior to delivery the fetus is at increased risk of intrauterine distress and sudden intrauterine death. The genetic etiology of most cases of ICP is unknown, although heterozygous carriers of mutations causing progressive familial intrahepatic cholestasis (PFIC) diseases may experience ICP. When examining linkage to known cholestasis genes, affected members of four Finnish ICP families shared haplotypes around ATP8B1, the gene responsible for PFIC1. This gene was subsequently screened in 176 familial and sporadic ICP patients. A total of 17 sequence changes were detected, five exonic and 12 intronic. No intronic change was associated with ICP in sporadic cases. Four intronic changes segregated with ICP in three families, a different change in each of two families and three changes in another family, although the significance of this is currently unknown. Three exonic changes were nonsynonymous, one (in exon 23) is probably a polymorphism while two predict novel amino-acid replacements (N45T and K203R). These changes, in exons 2 and 7, were detected in one individual each, and may have predisposed these individuals to ICP. In conclusion, although the exon 2 and 7 changes may have functioned as risk alleles, ATP8B1 is probably not a major gene contributing to the occurrence of ICP. (+info)
Paucity of intrahepatic bile ducts in infancy--experience of a tertiary center.
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BACKGROUND: Intrahepatic cholestasis secondary to paucity of bile duct is an alteration of the anatomic integrity of the biliary tract. Can be defined only histologically and, clinically, two categories are recognized: syndromic and non-syndromic, where the prognosis is generally more severe. AIM: To evaluate the history, clinical and biochemical characteristics, etiology and improvement of children who have paucity of intrahepatic bile duct followed at tertiary center. PATIENTS AND METHODS: Eleven children with paucity of intrahepatic bile duct, followed at the Pediatric Hepatology Service of the University Hospital, Campinas, SP, Brazil, were evaluated in the period from 1986 to 2001. RESULTS: Among the patients, three presented the syndromic and eight the non-syndromic form (two with alpha-1-antitrypsin deficiency, one with lues, one secondary to sepsis, three with probable etiology by cytomegalovirus and one without a definite etiology). Referral ranged from 31 to 1185 days. Birth weights ranged from 1920 g to 3590 g. Most of the patients presented pale stools. The median bile duct/portal tract ratio was 0.14. The majority of the children presented a favorable follow-up, regardless of the form of presentation. CONCLUSION: Paucity of intrahepatic bile ducts should be considered in children with cholestasis and its differentiation from extrahepatic causes of neonatal cholestasis is important in order to avoid surgery. Diagnosis of non-syndromic form should not be regarded as unfavorable prognosis, as the evolution is probably related to the etiology in this form of presentation. (+info)
Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial.
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PURPOSE: Biliary cancer has a poor prognosis, and chemotherapy has had little impact. The objectives of this trial were to determine the response rate, time to disease progression, survival, and safety profile of the combination of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer. PATIENTS AND METHODS: Eligible patients had pathologically proven, locally advanced or metastatic adenocarcinoma arising from the intra- and extrahepatic bile ducts or gallbladder with no prior chemotherapy. Patients were treated on a 3-week cycle consisting of capecitabine at 650 mg/m(2) orally twice a day for 14 days and gemcitabine at a fixed dose of 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8. RESULTS: Forty-five patients were enrolled between July 2001 and January 2004. Fifty-three percent of patients had cholangiocarcinoma, 47% had gallbladder cancer, and 89% had metastatic disease. The overall objective response rate was 31%, with an additional 42% of patients with stable disease, for a disease control rate of 73%. The median overall survival time was 14 months (95% CI, 7.3 months to not available), and the median progression-free survival time was 7 months (95% CI, 4.6 to 11.8 months). This chemotherapy combination was generally well tolerated. Transient neutropenia, thrombocytopenia, fatigue, and hand-foot syndrome were commonly observed but were easily managed without discontinuing further treatment. CONCLUSION: The significant antitumor activity combined with a mild toxicity profile seen in this study argue that GemCap chemotherapy may benefit patients with advanced biliary cancer. This regimen warrants further evaluation in a randomized study with survival and quality of life end points. (+info)
Neonatal lupus erythematosus presenting with cholestatic hepatitis: a case report and review of the literature.
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Neonatal lupus erythematosus (NLE) is a disease primarily characterized by cardiac and/or cutaneous involvement. Hepatic, hematological, neurological and pulmonary involvement are rare manifestations and normally considered as mild and transient complications. But recent studies have shown more frequent hepatic involvement in NLE. We report a two month-old male infant, born to a clinically asymptomatic mother, presenting with significant hepatic involvement and annular, erythematous plaques with hyperkeratotic borders at the eyebrow region and anterior surface of trunk. Both the infant and his mother were positive for anti-Ro (SS-A) and anti-La (SS-B). (+info)
ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy.
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BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) affects approximately 0.7% of pregnancies in the UK and is associated with prematurity, fetal distress, and intrauterine death. Homozygous mutations in the ATP8B1 gene cause cholestasis with a normal serum gamma-glutamyl transpeptidase (gamma-GT), and have been reported in two forms of cholestasis: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC). AIMS: To establish whether mutations in ATP8B1 are associated with ICP in British cases PATIENTS: Sixteen well phenotyped women with ICP without raised gamma-GT were selected for sequence analysis. Subsequently, 182 patients and 120 controls were examined for the presence of the variants detected. METHODS: All coding exons were sequenced in 16 cases. Eight ICP cases, including two women carrying a mutation, were investigated using in vivo hepatic (31)P magnetic resonance spectroscopy (MRS) RESULTS: Two heterozygous ATP8B1 transitions (208G>A and 2599C>T) that resulted in amino acid substitutions were identified; 208G>A was identified in three cases. MRS revealed an increased phosphodiester signal (Mann-Whitney U test, p = 0.03) and a decreased phosphomonoester/phosphodiester ratio (p = 0.04) in ICP cases compared with controls. CONCLUSIONS: We were able to demonstrate ATP8B1 mutations in ICP. MRS studies suggest that susceptibility to ICP is associated with a relative rise in biliary phospholipid. These data also suggest that MRS may be used for non-invasive assessment of the liver and biliary constituents in cholestasis. (+info)