BetaKlotho: a new kid on the bile acid biosynthesis block.
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Animals↗
Biomedical subjects
Marco Arrese
Publications and source records attributed to Marco Arrese.
Value of adenosine deaminase (ADA) in ascitic fluid for the diagnosis of tuberculous peritonitis: a meta-analysis.
BACKGROUND AND GOALS: Adenosine deaminase (ADA) levels are used for diagnosing tuberculosis in several locations and although many studies have evaluated ADA levels in ascitic fluid. These studies have defined arbitrary cut-off points creating difficulties in the clinical application of the results. The goals of this study are: to determine the usefulness of ADA levels in ascitic fluid as a diagnostic test for peritoneal tuberculosis (PTB) and define the best cut-off point. STUDY: A systematic review was done on the basis of 2 independent searches. We selected prospective studies that included consecutive patients. Diagnosis of PTB had to be confirmed by bacteriologic or histologic methods and ADA levels determined by the Giusti method. Inclusion/exclusion criteria were applied by 2 independent reviewers. A receiver operating characteristic curve was constructed to establish the optimal cut-off point and the likelihood ratios (LRs) estimated using fixed-effect pooled method. RESULTS: Twelve prospective studies were found. Four of them met the inclusion criteria and were thus included in the meta-analysis. They included 264 patients, of which 50 (18.9%) had PTB. ADA levels showed high sensitivity (100%) and specificity (97%) using cut-off values from 36 to 40 IU/L. The included studies were homogeneous. Optimal cut-off point was determined at 39 IU/L, and LRs were 26.8 and 0.038 for values above and below this cut-off. CONCLUSIONS: This study supports the proposition that ADA determination is a fast and discriminating test for diagnosing PTB with an optimal cut-off value of 39 IU/L.
Adenosine Deaminase↗
Successful liver transplantation and delivery in a woman with fulminant hepatic failure occurring during the second trimester of pregnancy.
BACKGROUND: Severe liver dysfunction occurring during pregnancy is an unusual but dramatic event that poses special technical and ethical issues because it involves two lives. METHODS AND RESULTS: We report the case of a 35-year-old woman with cryptogenic fulminant hepatic failure who underwent successful orthotopic liver transplantation at 22 weeks of pregnancy. After a relatively uneventful post-operative course she delivered a normal offspring at the 27th week of gestation. There were no obstetrical complications and neonatal outcome was excellent. After a year of follow-up, the patient is doing well,and the newborn has exhibited normal psychomotor and weight/height development. CONCLUSION: This case illustrates the challenge of treating fulminant hepatic failure during pregnancy and demonstrates that liver transplantation is a feasible therapeutic option for treatment of patients with this condition, allowing successful completion of pregnancy.
Adult↗
Increased orocecal transit time in patients with nonalcoholic fatty liver disease.
Intestinal bacterial overgrowth (IBO) has been suggested to play a pathogenic role in patients with nonalcoholic fatty liver disease (NAFLD). Delayed intestinal transit may contribute to IBO development. Ten nondiabetic patients with NAFLD and abnormal liver enzymes were recruited. Ten healthy individuals, matched by sex, age, and body mass index, were used as controls. Orocecal transit time (OCTT) was measured by the lactulose breath test. Anti-endotoxin core antibodies (EndoCAb) were determined. The effect of oral norfloxacin (400 mg BID during 2 weeks) on liver enzymes, lactulose breath test, and EndoCAb was also studied. NAFLD patients had higher basal breathed H2 and prolonged OCTT compared to controls (127 +/- 61 vs. 57 +/- 23 min, respectively; P = 0.0037). EndoCAb titers were similar in NAFLD patients and controls. Norfloxacin administration had no effect on ALT levels, lactulose breath test, or EndoCAb titers in patients with NAFLD. The present data show evidence of deranged intestinal motility in nondiabetic patients with NAFLD and support the hypothesis that NAFLD could be linked to endotoxin-induced liver damage of intestinal origin.
Adult↗
Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass.
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are conditions gaining increasing recognition in hepatology as a potential cause of cirrhosis and end-stage liver disease. Obesity is one of the main risk factors. The aims of this study were to determine the frequency of NAFLD in obese patients and to identify variables that predict NASH. METHODS: A prospective study was conducted of obese patients undergoing gastric bypass over a 20-month period. Assessment included liver function tests and evaluation of insulin resistance with the homeostatic model assessment (HOMA-IR). Liver biopsy was performed in all patients at the time of surgery. Clinical and biochemical variables were analyzed using a multivariate analysis to identify independent predictors of NASH. RESULTS: 127 consecutive patients were included (62% female, 38% male, mean age 40+/-11 years, mean body mass index 42+/-6 kg/m(2)). Arterial hypertension was present in 52 patients (41%) and type 2 diabetes in 18 (14%). NAFLD was confirmed in 80 patients (63%), 47 (37%) had simple steatosis, and 33 (26%) had NASH. Cirrhosis was found in 2 patients corresponding to 1.6% of the total population. On multivariate analysis, AST >31 (IU/L) (OR 3.38, CI 1.17-9.8) and HOMA-IR >5.8 (OR 4.18, CI 1.39-12.49) independently predicted NASH. CONCLUSIONS: NAFLD is highly prevalent in morbidly obese patients. A high proportion of these patients exhibit NASH on histological examination. Insulin resistance represents the main predictor of NASH.
Adult↗
The bile salt export pump: molecular properties, function and regulation.
Secretion of bile salts from the hepatocyte into bile is the major driving force for the generation of bile flow. Identification of the bile salt export pump (BSEP, ABCB11) as the main adenosine-triphosphate-dependent bile salt transporter in mammalian liver has led to a greater understanding of the biliary bile salt secretory process and its regulation. The biology and pathobiology of BSEP have been the subject of many recent studies. Thus, it has been recognized that while mutations in the gene encoding BSEP are responsible for a subgroup of progressive familial cholestasis (progressive familial intrahepatic cholestasis subtype 2), a pediatric cholestatic disorder that may progress to cirrhosis, defective expression or function of BSEP may underlie some forms of drug-induced cholestasis. The present review summarizes recent data on the molecular properties and regulation of BSEP, as well as the clinical implications of absent or defective function of this hepatic efflux pump.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Histological resolution of steatohepatitis after iron depletion.
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Fatty Liver↗
[Outpatient laparoscopic cholecystectomy. Experience in 357 patients].
BACKGROUND: Laparoscopic cholecystectomy (LC) is a widely used technique in the treatment of gallstone disease. Outpatient laparoscopic cholecystectomy (OLC) is a cost/effective and safe procedure in selected patients. AIM: A pilot program of OLC was conducted in a Chilean Public Hospital to evaluate the feasibility and results, including and patients' satisfaction using OLC. PATIENTS AND METHODS: Patients were eligible for OLC if they were less than 60 years old, had low anesthestetitc risk (ASA I-II), normal liver function tests and an abdominal ultrasound showing gallstones or gallbladder polyps with a normal common bile duct. RESULTS: We performed OLC in 357 patients aged 36 +/- 10 years, 90% female. Intraoperative complications were observed in 4 (1.1%) patients (uncontrolled bleeding in two and minor biliary tree injuries in two, both requiring conversion to the open technique). Four other patients required conversion due to anatomic reasons (overall conversion rate: 2.2%). Ninety two percent of patients were discharged within 6 hours of the operation. Eight (2.2%) were readmitted because of a mild acute pancreatitis (n=1), biliary leakage (n=1), persistent pain (n=2), vomiting (n=2), and retained stones (n=2). Two (0.6%) patients were re-operated. There was no mortality. Ninety-four percent of 277 patients (77.6%), who answered a Satisfaction Survey, evaluated OLC procedure with a high degree of satisfaction. CONCLUSION: OLC is a safe and feasible procedure in selected gallstone patients. The procedure has good outcomes and a high degree of patient satisfaction. A wide use of OLC should reduce both direct and indirect costs of surgical treatment of gallstone disease.
Adolescent↗
Hepatic overexpression of caveolins increases bile salt secretion in mice.
Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes, including cholesterol transport. Because hepatocytes express caveolin-1 and caveolin-2, these proteins might modulate hepatic lipid metabolism and biliary lipid secretion. Our aim was to investigate the potential physiologic role of caveolins in hepatic cholesterol and bile salt (BS) metabolism and transport using adenoviral gene transfer. C57BL/6 mice were infected with recombinant human caveolin-1 and caveolin-2 adenoviruses. Mice infected with adenovirus lacking the transgene were used as controls. Hepatic caveolin expression was evaluated by immunochemical methods. Reverse-transcription polymerase chain reaction (RT-PCR) and immunoblotting were used to assess messenger RNA (mRNA) levels and protein mass of BS transporters (sodium taurocholate cotransporting polypeptide [Ntcp] and bile salt export pump [Bsep]). Serum, liver, biliary, and fecal biochemical determinations and BS maximal secretory rate (SRm) were performed by standard methods. Ad.Cav-1- and Ad.Cav-2-infected mice exhibited a 10- and 7-fold increase in hepatic caveolin-1 and caveolin-2 protein expression, respectively. Caveolin-1-overexpressing mice had a significant increase in plasma high-density lipoprotein (HDL) cholesterol and hepatic free cholesterol content, whereas total plasma cholesterol and triglyceride levels remained unchanged. Hepatic caveolin-1 and/or caveolin-2 overexpression significantly increased bile flow and secretion of all biliary lipids. Caveolin-1-overexpressing mice showed a 2.5-fold increase in taurocholate (TC) SRm, indicating increased canalicular BS transport capacity. BS pool size and fecal BS excretion remained within the normal range in mice with Cav-1 overexpression. No changes were seen in the protein mass of BS transporters Ntcp and Bsep. In conclusion, our findings indicate that caveolins may play an important role in regulating hepatic BS and cholesterol metabolism.
Adenoviridae↗
Molecular aspects of bile formation and cholestasis.
Recent insights into the cellular and molecular mechanisms that control the function and regulation of hepatobiliary transport have led to a greater understanding of the physiological significance of bile secretion. Individual carriers for bile acids and other organic anions in both liver and intestine have now been cloned from several species. In addition, complex networks of signals that regulate key enzymes and membrane transporters located in cells that participate in the metabolism or transport of biliary constituents are being unraveled. This knowledge has major implications for the pathogenesis of cholestatic liver diseases. Here, we review recent information on molecular aspects of hepatobiliary secretory function and its regulation in cholestasis. Potential implications of this knowledge for the design of new therapies of cholestatic disorders are also discussed.
Animals↗
Down-regulation of the Na+/taurocholate cotransporting polypeptide during pregnancy in the rat.
BACKGROUND: Experimental studies have shown decreased bile acid (BA) uptake and reduced excretion of cholephilic compounds in pregnant rodents. AIM: To assess the expression and function of the main BA importer, the Na(+)/taurocholate cotransporting polypeptide (Ntcp) in pregnant rats. METHODS: BA uptake and Ntcp expression were studied in control and timed-pregnant rats in late gestation. Ntcp protein, messenger RNA (mRNA) expression, and Ntcp tissue localization were determined by Northern blotting, Western analysis, and tissue immunofluorescence. The activity of three transactivators of the Ntcp promoter: hepatocyte nuclear factor 1-alpha (HNF1-alpha), nuclear receptor heterodimer retinoid X receptor:retinoid acid receptor (RXR:RAR) and signal transducer and activator of transcription 5 (Stat5) was assessed using gel electrophoretic mobility shift assays. RESULTS: A significantly reduced BA uptake and decreased Ntcp mRNA levels (-40%) and protein mass (-60%) was observed in pregnant rats. Nuclear extracts from pregnant rats showed a marked decrease of HNF1-alpha and RXR:RAR binding activities by -80 and -40% of basal activity, respectively. In contrast, binding activity of Stat-5 was increased by 50% in nuclear extracts from pregnant rats. CONCLUSIONS: Pregnancy is associated with reduced Ntcp expression and function in the rat. Our findings suggest that Ntcp down-regulation during pregnancy occurs primarily at the transcriptional level.
Animals↗
Is intrahepatic cholestasis of pregnancy an MDR3-related disease?
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ATP Binding Cassette Transporter, Subfamily B↗
Bile secretory function after warm hepatic ischemia-reperfusion injury in the rat.
Hepatic ischemia-reperfusion (I-R) injury frequently is associated with cholestasis. However, the underlying mechanisms are not fully understood. The aim of the study is to assess bile secretory function in vivo in rats subjected to warm lobar hepatic ischemia at different times during reperfusion. A model of lobar 70% warm hepatic ischemia for 30 minutes was used with studies conducted at 1 and 6 hours and 1, 3, and 7 days after reperfusion. Bile secretory function was assessed after selective cannulation of bile ducts of ischemic (ILs) and nonischemic lobes (NILs). Serum activity of hepatic alanine and aspartate aminotransferase was slightly increased in rats subjected to I-R, whereas serum bile salt levels increased early during reperfusion, returning to control values after 7 days. ILs showed mild reversible leukocyte infiltration and no significant necrosis. Bile flow and bile salt excretion were significantly decreased in ILs during the first 24-hour reperfusion period compared with sham-operated rats and NILs. A marked reduction in glutathione (GSH) excretion occurred at 1 and 6 hours and 1 and 3 days, which returned to control values after 7 days. Total GSH and both reduced and oxidized GSH levels in liver homogenate and arterial blood GSH levels were unchanged at all times. Protein mass of multidrug resistance protein 2 and its function, assessed by the hepatic maximum secretory rate of ceftriaxone, did not show significant changes in ILs or NILs compared with sham-operated rats. Liver tissue gamma-glutamyl transpeptidase (GGT) and gamma-glutamylcysteine synthetase activities remained unchanged, whereas biliary GGT and cysteine secretory rates were significantly increased in ILs and NILs. Administration of acivicin, a GGT inhibitor, resulted in decreased secretion of this enzyme into bile and a parallel marked increase in biliary GSH secretion compared with untreated ischemic rats. In conclusion, warm hepatic I-R induces reversible cholestatic changes in ILs. GSH secretory rates from both ILs and NILs were markedly decreased during reperfusion. The reversibility of this effect after GGT inhibition, as well as increased release of active GGT into bile and cysteine biliary secretory rates, suggest increased GSH degradation in bile. These findings might be relevant for the I-R-induced clinical cholestasis, as well as cholangiocyte injury, seen after hepatic ischemia.
Animals↗
Saccharomyces cerevisiae fungemia after Saccharomyces boulardii treatment in immunocompromised patients.
Saccharomyces cerevisiae is widely used as a probiotic compound. Clinical data suggest that this agent is safe and effective. We report two cases of fungemia caused by S. cerevisiae occurring in immunosuppressed patients treated orally with S. boulardii Molecular typing confirmed clonality in isolate strains from patients and the capsule. Physicians caring for immunosuppressed patients must be aware of this potential serious complication of probiotic use.
Adult↗
HNF-1 alpha: have bile acid transport genes found their "master"?
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Carrier Proteins↗
From blood to bile: recent advances in hepatobiliary transport.
Transport of endogenous and exogenous substances from blood to bile is an essential function of the liver. In the last decade a still growing number of specific transport proteins present at the sinusoidal and canalicular membrane domains of hepatocytes and cholangiocytes have been cloned and functionally characterized. Studies assessing the molecular expression and function of these hepatobiliary transport proteins under different experimental conditions has helped to define the adaptive responses of hepatocytes to certain physiological states and to cholestatic liver injury and to a better understanding of the physiology of bile formation and of the pathophysiology of certain cholestatic diseases. Particularly relevant is the elucidation of the molecular bases of several forms of inherited cholestatic liver disease, which may help to the development of better diagnostic tools or to the design of new therapeutic strategies. In the present review we summarize recent experimental and clinical data involving hepatobiliary transport mechanisms.
ATP-Binding Cassette Transporters↗
Clinical and epidemiological features of 147 Chilean patients with chronic hepatitis C.
Prevalence, modes of transmission, clinical characteristics and outcomes of hepatitis C (HCV) infection vary in different geographical areas. We aim to describe clinical and epidemiological features of Chilean patients infected with hepatitis C virus. An analysis of demographic, epidemiological, clinical and laboratory data of patients referred to a liver clinic and blood donors with chronic hepatitis C was carried out. 147 patients were evaluated, 68 (46%) were male. Median age was 56 years, median infection age was 27 years and median duration of infection was 27 years. 52.5% of the patients were cirrhotic, and estimated risk of progression to cirrhosis was 16% at 20 years from infection. Risk factors for acquisition of the disease among patients were: Blood transfusion 54%, injection drug use 5%, and risky sexual behavior 2%. No factor was identified in 43% of the patients. Twelve of 64 (18.8%) family members tested positive for HCV antibodies. Genotype 1b was predominant (82%), and 52% of patients had high viral load (>850.000 IU/mL). Liver biopsy was available in 50 patients, showing advanced fibrosis in 54%. These patients were in average 10 years older and tended to have longer duration of infection. Hepatocellular carcinoma was present at the moment of enrollment in 7 patients and developed in 4 more patients during follow up (2.4 years). In conclusion, the natural history and clinical characteristics of HCV infection in Chilean patients is similar to that described elsewhere. The main risk factor was blood transfusion. A significant proportion of patients had advanced liver disease or hepatocellular carcinoma at time of diagnosis.
Adult↗
Incidence and prevalence of hepatitis C virus infection in Chile.
UNLABELLED: Chronic hepatitis C is a major cause of liver-related morbidity and mortality. Epidemiological data regarding this infection in developing countries is scanty. METHODS: Prevalence of hepatitis C (HCV) infection was investigated in a random sample of Chilean general adult population older than 20 years of age. Additionally, frequency of HCV infection was assessed in group of native Chilean Amerindians (Mapuche Indians) living in an isolated locality of the Southern Chile. Incidence of HCV infection was estimated using serum samples separated by 7 years (1993-2000). RESULTS: Among 959 subjects, prevalence of anti-HCV antibodies was 1.15% (95% CI 0.48-1.82%) and 0.83% when only RIBA-confirmed cases were considered. Among these subjects, 62.5% had detectable HCV RNA in serum and 40% of them had a history of blood transfusion. Age distribution of cases showed a steadily increasing prevalence with age. Estimated incidence of new HCV infections was 15 per 100,000 subjects per year in the period 1993-2000. No cases were detected among the 145 Mapuche subjects studied. CONCLUSIONS: HCV infection is a prevalent disease in the Hispanic population of Chile with a low incidence in the last decade, whereas it was not detected in an isolated Mapuche Indian community. Age distribution of prevalence suggests that the peak of infection in Chile occurred 30 to 50 years ago.
Adult↗