Fasting Serum Bile Acid Research Articles

The development of hepatic steatosis depends on the presence of liver-innervating parasympathetic cholinergic neurons in mice fed a high-fat diet.

Hepatic lipid metabolism is regulated by the autonomic nervous system of the liver, with the sympathetic innervation being extensively studied, while the parasympathetic efferent innervation is less understood despite its potential importance. In this study, we investigate the consequences of disrupted brain-liver communication on hepatic lipid metabolism in mice exposed to obesogenic conditions. We found that a subset of hepatocytes and cholangiocytes are innervated by parasympathetic nerve terminals originating from the dorsal motor nucleus of the vagus. The elimination of the brain-liver axis by deleting parasympathetic cholinergic neurons innervating the liver prevents hepatic steatosis and promotes browning of inguinal white adipose tissue (ingWAT). The loss of liver-innervating cholinergic neurons increases hepatic Cyp7b1 expression and fasting serum bile acid levels. Furthermore, knockdown of the G protein-coupled bile acid receptor 1 gene in ingWAT reverses the beneficial effects of the loss of liver-innervating cholinergic neurons, leading to the reappearance of hepatic steatosis. Deleting liver-innervating cholinergic neurons has a small but significant effect on body weight, which is accompanied by an increase in energy expenditure. Taken together, these data suggest that targeting the parasympathetic cholinergic innervation of the liver is a potential therapeutic approach for enhancing hepatic lipid metabolism in obesity and diabetes.

The development of hepatic steatosis depends on the presence of liver-innervating parasympathetic cholinergic neurons in mice fed a high-fat diet.

Hepatic lipid metabolism is regulated by the autonomic nervous system of the liver, with the sympathetic innervation being extensively studied, while the parasympathetic efferent innervation is less understood despite its potential importance. In this study, we investigate the consequences of disrupted brain-liver communication on hepatic lipid metabolism in mice exposed to obesogenic conditions. We found that a subset of hepatocytes and cholangiocytes are innervated by parasympathetic nerve terminals originating from the dorsal motor nucleus of the vagus. The elimination of the brain-liver axis by deleting parasympathetic cholinergic neurons innervating the liver prevents hepatic steatosis and promotes browning of inguinal white adipose tissue (ingWAT). The loss of liver-innervating cholinergic neurons increases hepatic Cyp7b1 expression and fasting serum bile acid levels. Furthermore, knockdown of the G protein-coupled bile acid receptor 1 gene in ingWAT reverses the beneficial effects of the loss of liver-innervating cholinergic neurons, leading to the reappearance of hepatic steatosis. Deleting liver-innervating cholinergic neurons has a small but significant effect on body weight, which is accompanied by an increase in energy expenditure. Taken together, these data suggest that targeting the parasympathetic cholinergic innervation of the liver is a potential therapeutic approach for enhancing hepatic lipid metabolism in obesity and diabetes.

Diagnostic utility of serum bile acids in dogs presenting with epileptic seizures consistent with a tier 1 confidence level diagnosis of idiopathic epilepsy.

The International Veterinary Epilepsy Task Force consensus guidelines recommend performing fasting serum bile acid (SBA) and/or serum ammonia measurements as part of a tier 1 diagnosis of idiopathic epilepsy in dogs. The aim of this retrospective study was to determine the diagnostic utility of fasting SBA in this population. Dogs that met the tier 1 confidence level diagnosis of idiopathic epilepsy, with the additional requirement of both fasting and 2-hour postprandial SBA measurements, were included. The incidence of significant hepatopathies and usefulness of dynamic SBA testing and minimum database results were analysed. A total of 233 dogs were included. All dogs diagnosed with clinically significant hepatopathy had elevations in postprandial SBA, with eight of 14 (57.14%) showing elevations in fasting SBA. The prevalence of clinically significant hepatopathies that could have been missed without using postprandial SBA measurement was 1.29%. The further investigations performed were not uniform and there were limitations in the ability to control sampling techniques due to the retrospective nature of this study. Investigations into hepatopathy were not standardised across this study population. This study documents the importance of postprandial SBA measurements in the detection of hepatopathies and revealsthat non-dynamic blood sampling has a negative predictive value of 91% for detecting elevated postprandial SBA, specific to dogs meeting the tier 1 confidence level diagnosis of idiopathic epilepsy.

Intrahepatic cholestasis of pregnancy - Time to redefine the reference range of total serum bile acids: A cross-sectional study.

ObjectiveTo establish pregnancy‐specific reference ranges for fasting and postprandial total serum bile acid (TSBA) concentrations.DesignCross‐sectional study.SettingTertiary‐care university hospital.PopulationHealthy pregnant women at term admitted to the Obstetrics Department over a period of 1 year. Exclusion criteria were an established diagnosis of intrahepatic cholestasis of pregnancy (ICP) or any coexisting condition of increased risk for ICP.MethodsBoth fasting (after 8–14 h of fasting) and postprandial (2 h after meal) TSBA concentrations were measured in 612 women (with 528 fasting samples and 377 postprandial samples) by automated enzymatic spectrophotometric assay.Main outcome measuresFasting and postprandial TSBA concentrations in 612 women.ResultsReference intervals of 4.4–14.1 μmol/L for fasting TSBA and 4.7–20.2 μmol/L for postprandial TSBA were established. The postprandial values were significantly higher than the fasting values, with a median increase of 1.0 μmol/L (p < 0.0001). A correlation between fasting TSBA concentrations and postprandial concentrations was found, as well as correlations with fetal sex, parity and assisted reproductive technologies. A seasonal pattern was noticed for both fasting and postprandial TSBA, with the highest values measured in the winter season (p < 0.01 and 0.02, respectively)ConclusionsNormal pregnancy is associated with mild hypercholanaemia, and therefore a higher threshold should be considered for the diagnosis of ICP. We suggest using the upper reference limits observed in our healthy pregnant population (14 μmol/L for fasting TSBA and 20 μmol/L for postprandial TSBA). As the fasting measurement is more specific for the diagnosis, and the postprandial measurement is essential for the assessment of severity, it is recommended to measure both values rather than use random sampling.Tweetable abstractNormal pregnancy is associated with mild hypercholanaemia, a higher threshold should be considered for the diagnosis of ICP.

Increased serum delta neutrophil index levels are associated with intrahepatic cholestasis of pregnancy.

This study aims to compare the maternal serum delta neutrophil index (DNI) levels in intrahepatic cholestasis of pregnancy (ICP) and healthy pregnancies. This study consisted of a group of patients (n=40) diagnosed with isolated ICP who gave birth in our hospital and a control group (n=60) between December 1, 2015, and June 30, 2018. The diagnosis of ICP was made based on pruritus and elevated fasting serum bile acids and liver enzymes. Laboratory tests of both groups in the hospitalization process were retrospectively examined. Maternal and neonatal characteristics, pregnancy outcomes, and DNI values of the two groups were compared. Statistical analyses were performed using SPSS version 20. Mean maternal serum DNI levels were significantly higher in women with ICP than in the control group (0.49 ± 4.8 vs -3.99 ± 3.02, p=<0.01). Receiver operating characteristic (ROC) curve analysis was used to define the DNI value where ICP can be best predicted. DNI, a new inflammatory marker, was found to be higher in women with ICP than in normal pregnancies.

Relationship between pruritus and autotaxin in intrahepatic cholestasis of pregnancy

ObjectiveIntrahepatic cholestasis of pregnancy is a temporary, pregnancy-specific disease that resolves with delivery, characterized by itching (pruritus), as well as high transaminase and serum bile acid levels in the third trimester of pregnancy. Due to the effects of Autotaxin on the physiology of pregnancy, we aimed to investigate Autotaxin activity in patients with intrahepatic cholestasis of pregnancy. Patients and methodsSixty-nine patients diagnosed with intrahepatic cholestasis of pregnancy and 20 healthy pregnant women were enrolled in the study. Fasting serum bile acid, pruritus intensity, serum parameters, gestational week of the patients at the time of diagnosis were recorded, and birth week and birth weight were monitored. Autotaxin serum level was measured enzymatically. ResultsThe mean serum bile acid level (n=69; 38.74±35.92μmol/L) in patients with intrahepatic cholestasis of pregnancy (n=69) was detected to be higher than healthy pregnant women (n=20; 5.05±1.88μmol/L) (p<0.001). Weak correlation was detected between serum bile acid level and itch intensity (p=0.014, r=0.295), while no relation was detected between Autotaxin and itch intensity (p=0.446, r=0.09). Although mean Autotaxin (intrahepatic cholestasis of pregnancy: 678.10±424.42pg/mL, control: 535.16±256.47pg/mL) levels were high in patients with intrahepatic cholestasis of pregnancy, it was not statistically significant (p=0.157). ConclusionIn our study, we observed that the serum Autotaxin level did not make a significant difference in patients with intrahepatic cholestasis of pregnancy compared to healthy pregnant women. These findings suggest that larger clinical studies are required to reveal the physio-pathological effects of Autotaxin on pregnancy.

The role of genetic mutations in intrahepatic cholestasis of pregnancy

ObjectiveIntrahepatic cholestasis of pregnancy (ICP) is a liver disorder of pregnancy characterized by pruritus, elevated liver enzymes and fasting serum bile acids. Genetic predisposition has been suggested to play a role in its etiology and mutations in the ATP8B1(OMIM ∗602397) (FIC1), ABCB11(OMIM ∗603201) (BSEP), and ABCB4(OMIM ∗171060) (MDR3) genes have been implicated.In the present study, we aimed to investigate the possible role of ATP8B1, ABCB11, and ABCB4 gene mutations in the patients with ICP. Materials and methodsA total of 25 patients who were diagnosed with ICP were included in the study. Genetic test results and mutation status of the patients as assessed by the next-generation sequencing technology were retrospectively retrieved from the hospital database. ResultsOf all patients, significant alterations in the ATP8B1 (n = 2), ABCB11 (n = 1), and ABCB4 (n = 7) genes were observed in 10 patients using the molecular analysis testing. All these alterations were heterozygous. Of these alterations, four were reported in the literature previously, while six were not. Using the in-silico parameters, there was a pathogenic alteration in the ABCB4 gene in one patient, while there was no clinically relevant alteration in the other gene mutations in the remaining nine patients. ConclusionConsidering the fact that the alterations were compatible with clinical presentations of the ICP patients and the incidence of these mutations is low in the general population, we believe that our study results are clinically relevant. Further molecular genetic tests in ICP patients and functional studies supporting the results would shed light into the clinical importance of these alterations.

Fasting serum bile acids concentration is associated with insulin resistance independently of diabetes status.

Background Bile acids (BAs) have been demonstrated to exert a variety of metabolic effects and alterations in BAs have been reported in patients with obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM). However, it is unclear which metabolic condition is the main contributor to alterations in BAs. In this study, we investigate the associations between different BA profiles with glycemia, obesity or IR status. Methods Fasting serum concentrations of 15 BA species were determined in a total of 241 individuals (71 drug-naïve patients with T2DM, 95 patients with impaired fasting glucose [IFG], and 75 healthy controls. Results A comparison of the mean values of the BAs revealed no significant differences between normoglycemic controls and patients with IFG or T2DM. However, when the entire cohort was divided according to the presence of IR as determined by a homeostasis model assessment of insulin resistance (HOMA-IR) value >2.5, the levels of total BA and most species of BAs were significantly higher in patients with IR than in patients without. In the correlation analysis, most species of BAs, as well as total BA, were significantly associated with HOMA-IR levels. Furthermore, when the subjects were divided into four groups according to IR and diabetic status, subjects with IR had significantly higher total BAs than participants without IR both in diabetic and non-diabetic groups. Ultimately, multiple linear regression analysis identified HOMA-IR as the only significant contributor to most serum BA species. Conclusions Our findings support the essential role of IR in regulating BA metabolism and that this effect is independent of diabetic status.

Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus.

Pruritus is a common symptom in patients with primary biliary cholangitis (PBC) for which ileal bile acid transporter (IBAT) inhibition is emerging as a potential therapy. We explored the serum metabonome and gut microbiota profile in PBC patients with pruritus and investigated the effect of GSK2330672, an IBAT inhibitor. We studied fasting serum bile acids (BAs), autotaxin and faecal microbiota in 22 PBC patients with pruritus at baseline and after 2weeks of GSK2330672 treatment. Control group included 31 asymptomatic PBC patients and 18 healthy volunteers. BA profiling was done by ultra performance liquid chromatography coupled to a mass spectrometry (UPLC-MS). Faecal microbiomes were analysed by 16S ribosomal RNA gene sequencing. In PBC patients with pruritus, serum levels of total and glyco-conjugated primary BAs and autotaxin were significantly elevated. Autotaxin activity correlated significantly with tauro- and glyco-conjugated cholic acid (CA) and chenodeoxycholic acid (CDCA), both at baseline and after GSK2330672. GSK2330672 significantly reduced autotaxin and all tauro- and glyco- conjugated BAs and increased faecal levels of CA (P=0.048) and CDCA (P=0.027). Gut microbiota of PBC patients with pruritus was similar to control groups. GSK2330672 increased the relative abundance of Firmicutes (P=0.033) and Clostridia (P=0.04) and decreased Bacteroidetes (P=0.033) and Bacteroidia (P=0.04). Pruritus in PBC does not show a distinct gut bacterial profile but is associated with elevated serum bile acid and autotaxin levels which decrease after IBAT inhibition. In cholestatic pruritus, a complex interplay between BAs and autotaxin is likely and may be modified by IBAT inhibition.

Effects of Duodenal-Jejunal Exclusion and New Bilio-Pancreatic Diversion on Blood Glucose in Rats with Type 2 Diabetes Mellitus.

The current study aimed to investigate the effects of duodenal-jejunal bypass (DJB), new bilio-pancreatic diversion (NBPD), and duodenal-jejunal exclusion (DJE) on blood glucose in rats with type 2 diabetes mellitus (T2DM). Male Sprague Dawley rats were fed with high glucose, high fat food, and intraperitoneally injected with streptozotocin to establish a T2DM animal model. T2DM rats were randomly assigned into 4 groups: a sham group (n=8), DJB group (n=9), NBPD group (n=10), and DJE group (n=10). Body weight, 2-h postprandial glucose, oral glucose tolerance, fasting serum bile acid, 2-h postprandial serum bile acid, fasting insulin, 2-h postprandial insulin (INS), fasting glucagon-like peptide-1 (GLP-1), and 2-h postprandial GLP-1 were measured before and after surgery. Six weeks after surgery, the 2-h postprandial glucose in the DJB (16.1±6.7mmol/L) and NBPD (19.5±5.7mmol/L) groups decreased significantly compared to the sham group (25.8±4.9mmol/L) (P<0.05). There was no significant difference between the DJE (25.0±5.0mmol/L) and sham groups (P>0.05). Four weeks after surgery, fasting serum bile acid in the DJB group (60.6±11.4μmol/L) and NBPD group (54.4±7.64μmol/L) was significantly higher than that in the sham group (34.3±6.98μmol/L; P<0.05). However, fasting GLP-1, 2-h postprandial GLP-1, and insulin remained unchanged at different time points after surgery (P>0.05). Body weight remained stable after surgery in all 4 groups (P>0.05). NBPD plays a major role in the therapy of T2DM with DJB. NBPD may significantly increase fasting serum bile acid in T2DM rats, an action that may be one of the mechanisms underlying the therapeutic effects of DJB on T2DM.

THU-358 - Fasting serum bile acids profile and insulin resistance in healthy blood donors

THU-358 - Fasting serum bile acids profile and insulin resistance in healthy blood donors

Long-Term Ursodeoxycholic Acid Therapy Does Not Alter Lithocholic Acid Levels in Patients with Cystic Fibrosis with Associated Liver Disease

To evaluate the fasting and postprandial serum bile acid composition in patients with cystic fibrosis-associated liver disease (CFLD) after chronic administration of ursodeoxycholic acid (UDCA) (20mg/kg/day). The aim was to specifically focus on the extent of biotransformation of UDCA to its hepatotoxic metabolite, lithocholic acid, because of recent concerns regarding the safety of long-term, high-dose UDCA treatment for CFLD. Twenty patients with CFLD (median age 16years, range: 2.4-35.0) prescribed UDCA therapy for at least 2years were studied. Total and individual serum bile acids were measured by stable-isotope dilution mass spectrometry, in fasting and 2-hour postprandial samples taken during chronic UDCA (20mg/kg/day) administration. During chronic UDCA administration (median duration 8years, IQR: 6-16), UDCA became the predominant serum bile acid in all patients (median, IQR: 3.17, 1.25-5.56μmol/L) and chenodeoxycholic acid concentrations were greater than cholic acid (1.86, 1.00-4.70μmol/L vs 0.40, 0.24-2.71μmol/L). The secondary bile acids, deoxycholate and lithocholate, were present in very low concentrations in fasted serum (<0.05μmol/L). After UDCA administration, 2-hour postprandial concentrations of both UDCA and chenodeoxycholic acid significantly increased (P<.01), but no significant changes in serum lithocholic acid concentrations were observed. These data do not support recent suggestions that enhanced biotransformation of UDCA to the hepatotoxic secondary bile acid lithocholic occurs when patients with CFLD are treated with relatively high doses of UDCA.

Effect of 6-8 weeks of oral ursodeoxycholic acid administration on serum concentrations of fasting and postprandial bile acids and biochemical analytes in healthy dogs.

Ursodeoxycholic acid (UDCA) is commonly used for the treatment of hepatobiliary disease. UDCA is a bile acid that can be detected in the bile acid assay. Its effect on biochemical analytes is unknown. The aim of this study was to determine the effect of 6-8 weeks of UDCA administration on fasting and postprandial concentrations of serum bile acids (SBA), cholesterol, triglycerides, bilirubin, and liver enzyme activities in healthy dogs. Twenty healthy dogs received UDCA for 6-8 weeks. CBC, biochemistry profile, urinalysis, fasting and postprandial SBA, and hepatobiliary ultrasound examination were performed prior to starting UDCA (timepoint 0) and after 6-8 weeks of therapy, while animals were still receiving UDCA (timepoint 1). Timepoint 0 and timepoint 1 values were compared with a paired t-test. SBA were remeasured 72 hours after UDCA discontinuation. Only mean fasting SBA at timepoint 1 increased significantly (P = .03) from timepoint 0 (2.26 μmol/L at time 0 and 3.81 μmol/L at time 1) but were not elevated above the normal reference interval (0-9 μmol/L). Two dogs had timepoint 1 fasting SBA above the reference interval (10 and 11.7 μmol/L). One dog had timepoint 1 postprandial SBA above the reference interval at 20.1 μmol/L (reference interval 0-17 μmol/L). Repeat SBA 72 hours after UDCA discontinuation were normal. Long-term administration of UDCA to healthy dogs may increase fasting SBA above pretreatment values (typically within the reference interval). Long-term administration of UDCA to healthy dogs does not alter liver enzyme activities, and bilirubin, cholesterol, or triglyceride concentrations.

Discriminatory metabolic and inflammatory parameters in serum and omental adipose tissue of obese patients with different insulin sensitivity

ObjectiveMetabolically healthy obese phenotype is defined by high insulin sensitivity and lack of metabolic syndrome, parameters regulated by omental adipose tissue inflammation, ectopic fat deposition and adipose tissue dysfunction. Our study aimed to identify novel metabolic and inflammatory markers in serum and omental adipose tissue which characterize the “unhealthy” obese patients and distinguish them from obese patients with better metabolic profile. DesignCross-sectional study. PatientsSubjects included 75 obese patients undergoing bariatric surgery at the Tel-Aviv Medical Center (mean age 43.9 ± 13.9, mean BMI 41 ± 8.4). The HOMA median value was used as a cut-off to differentiate between patients with better or worse insulin resistance. MeasurementsDemographic data, fasting serum insulin, glucose, bile acids, serum metabolic and inflammatory markers were obtained. During the bariatric surgery, omental adipose tissue was harvested and analyzed for metabolic and inflammatory markers using qRT-PCR. Logistic regressions were used to calculate odds ratio and 95% confidence interval for the prediction of the metabolic profile. ResultsSerum markers that were significantly higher among the obese with HOMA >6 were total bile acids. In the omental adipose tissue the inflammatory markers TNFα and ADAM17 were significantly higher among obese patients with HOMA >6. In multivariate analysis, the strongest predictor for insulin resistance was ADAM17 (OR = 1.82, 1.06–3.14, P = 0.031). ConclusionsThe study highlighted the predictive value of serum bile acids in identifying obese patients at high risk. Secondly, omental adipose tissue ADAM17 was revealed as a novel and strongest independent predictor for higher insulin resistance in morbidly obese patients.

Intrahepatic cholestasis in pregnancy

Abnormal liver function tests occur in 3-5% of pregnancies, with many potential causes, including coincidental liver disease (most commonly viral hepatitis or gallstones) and underlying chronic liver disease. Pruritus in pregnancy is common, affecting 23% of pregnancies, of which a small proportion will have obstetric cholestasis. Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder characterized by pruritus with onset in the second or third trimester of pregnancy, elevated serum aminotransferases and bile acid levels, and spontaneous relief of signs and symptoms within two to three weeks after delivery. ICP is observed in 0.4-1% of pregnancies in most areas of Central and Western Europe and North America. Genetic and hormonal factors, but also environmental factors may contribute to the pathogenesis of ICP. Intrahepatic cholestasis of pregnancy increases the risk of preterm delivery (19­60%), meconium staining of amniotic fluid (27%), fetal bradycardia (14%), fetal distress (22-41%), and fetal loss (0.4-4.1%), particularly when associated with fasting serum bile acid levels >40 μmol/L. Important ICP-induced changes in serum profiles of amidated bile acids were observed, involving both a marked increase in cholic acid concentration and a shift towards a higher proportion of taurine-conjugated species. Ursodeoxycholic acid (10-20 mg/kg/d) is today regarded as the first line treatment for intrahepatic cholestasis of pregnancy. Delivery has been recommended in the 37-38th week when lung maturity has been established.

Bile acids and coagulation factors

To examine whether there is an association between bile acids and coagulation factors in children with chronic liver disease. Forty-five patients (age 2.8 months-18.8 years) were included in this cross-sectional observational study carried out at a single tertiary referral center. Coagulation factors, prothrombin time, albumin, and total fasting serum bile acids were analyzed. The international normalized ratio (INR) and the pediatric end-stage liver disease score were calculated. The 12 patients with bile acids more than 200 μmol/l showed a significant positive correlation between bile acids and factor V (FV), FVII, and prothrombin time (r(s) = 0.80, 0.72, 0.60, P<0.05) and a significant negative correlation between bile acids and INR (r(s) = -0.58, P<0.05). Conversely, in the group with bile acids less than 200 μmol/l, there was a significant negative correlation between bile acids and FVII and FIX (r(s) = -0.41 and -0.41, P<0.05) and a positive, albeit nonsignificant, correlation between bile acids and INR. No in-vitro analytical interference between bile acids and coagulation factors was found. Patients with bile acids more than 200 μmol/l had a significantly worse outcome than patients with lower levels of bile acids. A positive correlation was found between bile acids and coagulation factors in patients with bile acids more than 200 μmol/l. Coagulation factors may be questionable as prognostic markers in patients with markedly elevated bile acids.

Intra-hepatic cholestasis of pregnancy: A comprehensive review

Intra-hepatic cholestasis of pregnancy is a cholestatic disorder characterized by i) pruritus, with onset in the third trimester of pregnancy, without any primary skin lesions, ii) elevated fasting serum bile acids > 10 μmol/L (and elevated serum transaminases), iii) spontaneous relief of signs and symptoms within two to three weeks after delivery, and iv) absence of other disease that cause pruritus and jaundice. It is believed to be a multi-factorial disease with interplay between genetic, environmental and hormonal factors. Incidence is between 0.02% to 2.4% of all pregnancies; with wide geographical variations. Maternal prognosis is usually good but can result in adverse fetal outcomes like meconium staining of amniotic fluid, fetal bradycardia and even fetal loss. Response to anti-histaminic is poor. Of all the medical therapies that have been described for the treatment for IHCP, ursodeoxycholic acid has the best response in relieving pruritus in mother, and probably has a role in preventing even the perinatal complications. Timely diagnosis and treatment is urged in order to prevent fetal complications and an early delivery between 37 to 38 weeks should be contemplated in severe cases, especially once fetal lung maturity is attained.

Coexistence of Intrahepatic Cholestasis of Pregnancy Accompanied by Hepatitis B Flare in a Pregnant Woman and the Subsequent Development of Postpartum Thyroiditis and HBS Antigen Loss: A Case Report

A 23-year-old pregnant woman was admitted to our hospital due to pruritus and right upper quadrant pain. Her abdominal ultrasound revealed hepatomegaly and the fetal ultrasonography was normal. Her HBS antigen was positive and HBe antigen was negative. HBV-DNA level was 350,000 copies / ml. Coincidental hepatobiliary diseases in pregnancy were ruled out. The patient received a diagnosis of HBe antigen negative hepatitis B and tenofovir disoproxil 245 mg / day was prescribed. At a follow-up visit one month later, she reported no improvement in her pruritus. The levels of liver transaminases were near-normal and HBV DNA was zero. However, her biochemistry revealed raised alkaline phosphatase and gamma glutamyl transferase levels. Her consecutively calculated fasting serum bile acid levels were too high. A diagnosis of severe intrahepatic cholestasis of pregnancy associated with hepatitis B infection was made and a treatment of ursodeoxycholic acid 1000 mg / day was prescribed while she continued to take tenofovir disoproxil. She had a normal delivery and there were no adverse outcomes for the fetus. Several weeks later, she was readmitted with tremor and nervousness. Her TSH level was low and CRP level was high. The rest of the laboratory findings were normal and an ultrasonography of thyroid showed paranchymal heterogenity. The aggregate of findings was consistent with postpartum thyroiditis. Finally, L-thyroxine was initiated on a daily basis. Interestingly, at the week of 96, loss of Hepatitis B surface antigen was detected during tenofovir treatment. doi:10.4021/jmc594w

Conjugated Bile Acids Associate with Altered Rates of Glucose and Lipid Oxidation after Roux-en-Y Gastric Bypass

Laparoscopic Roux-en-Y gastric bypass (RYGB) induces a more favorable metabolic profile than expected by weight loss alone. In this study, we investigated the effect of RYGB on serum bile acid levels and their relation to clinical outcomes. We included 30 obese patients who underwent RYGB (BMI = 46.1 ± 5.9 kg/m(2)). Clinical measurements and laboratory determinations were performed before surgery and 1 year after surgery. Fasting serum bile acids were measured by an enzymatic method and individual bile acids were quantified by HLPC-tandem mass spectrometry. Indirect calorimetry was performed to measure the rates of energy expenditure and substrate oxidation. Fasting total serum bile acid levels increased twofold after RYGB (pre, 3.68 ± 2.03 vs. post, 7.06 ± 9.65 μmol/l, +92 %, p = 0.002). This increase in total bile acids was accompanied by a decrease in conjugated bile acids, which correlated with decreased glucose oxidation (r = 0.571, p = 0.002) and with increased lipid oxidation (r = -0.626, p = 0.0004). The change in taurine-conjugated bile acids correlated with altered DIO2 mRNA expression in adipose tissue (r = -0.498, p = 0.013) potentially linking bile acid conjugation to substrate oxidation through DIO2. Fasting serum bile acid levels increase after RYGB. More specifically, changes in bile acid conjugation after RYGB associate with altered energy metabolism.

Coexistence of Intrahepatic Cholestasis of Pregnancy Accompanied by Hepatitis B Flare in a Pregnant Woman and the Subsequent Development of Postpartum Thyroiditis and HBS Antigen Loss: A Case Report

A 23-year-old pregnant woman was admitted to our hospital due to pruritus and right upper quadrant pain. Her abdominal ultrasound revealed hepatomegaly and the fetal ultrasonography was normal. Her HBS antigen was positive and HBe antigen was negative. HBV-DNA level was 350,000 copies/ml. Coincidental hepatobiliary diseases in pregnancy were ruled out. The patient received a diagnosis of HBe antigen negative hepatitis B and tenofovir disoproxil 245 mg/day was prescribed. At a follow-up visit one month later, she reported no improvement in her pruritus. The levels of liver transaminases were near-normal and HBV DNA was zero. However, her biochemistry revealed raised alkaline phosphatase and gamma glutamyl transferase levels. Her consecutively calculated fasting serum bile acid levels were too high. A diagnosis of severe intrahepatic cholestasis of pregnancy associated with hepatitis B infection was made and a treatment of ursodeoxycholic acid 1000 mg/day was prescribed while she continued to take tenofovir disoproxil. She had a normal delivery and there were no adverse outcomes for the fetus. Several weeks later, she was readmitted with tremor and nervousness. Her TSH level was low and CRP level was high. The rest of the laboratory findings were normal and an ultrasonography of thyroid showed paranchymal heterogenity. The aggregate of findings was consistent with postpartum thyroiditis. Finally, L-thyroxine was initiated on a daily basis. Interestingly, at the week of 96, loss of Hepatitis B surface antigen was detected during tenofovir treatment. J Med Cases. 2012;3(4):240-242 doi: https://doi.org/10.4021/jmc594w