Leptin Influence Cholelithiasis Formation by Regulating Bile Acid Metabolism.

BACKGROUND: Bile acid metabolism is a contributing factor that promotes cholelithiasis. Recent studies have suggested novel roles of leptin in the formation of gallbladder stones (GS); however, no evidence confirmed the function of leptin in the formation of primary intrahepatic bile duct stones (PIBDS) . In the current study, the liver tissues of patients with GS and PIBDS were collected to check the mRNA and protein expression levels of BSEP. METHODS: L02 cells stimulated with leptin were served for the expression of OB-Rb, AMPKα2, and BSEP by quantitative-polymerase chain reaction (q-PCR), Western blot, and immunohistochemistry, respectively. RESULTS: The results showed that the level of serum leptin was higher in the GS group than in the control and PIBDS groups. Compared with the control group, the expression levels of OB-Rb, p-AMPKa2, and BSEP decreased significantly in the GS and PIBDS groups. In vitro, compared with the control cells, the protein levels of OB-Rb, p-AMPKa2, and BSEP increased in the L02 cells cultured with leptin. However, these enhancements disappeared when the cells were co-cultured with leptin plus Compound C. CONCLUSION: The present results suggest that cholelithiasis, especially the formation of PIBDS, was connected with leptin, which could regulate bile acid metabolism through the OB-Rb/AMPKa2/BSEP signaling pathway.

Biliary adverse events in acromegaly during somatostatin receptor ligands: predictors of onset and response to ursodeoxycholic acid treatment.

PURPOSE: Somatostatin receptor ligands (SRL) are the first-line medical treatment for acromegaly. Gallbladder alterations are one of most important SRL side effect, but according to some authors growth hormone hypersecretion itself is a risk factor for gallstones. This single center, longitudinal retrospective study evaluated the incidence and the predictors of biliary adverse events (BAE) in acromegaly during SRL therapy and their response to ursodeoxycholic acid (UDCA). METHODS: 91 acromegaly patients with indication to SRL were enrolled. Evaluations of acromegaly activity (GH, IGF-I, IGF-I/ULN) and metabolic profile were collected before starting treatment, yearly during follow-up and at BAE onset. In patients developing BAE we searched for predictors of UDCA effectiveness. RESULTS: 61.5% of patients developed BAE (58.9% cholelithiasis; 41.1% only sludge). IGF-I and IGF-I/ULN proved to be positive predictor of BAE, which occur about 5 years after SRL starting. None of metabolic markers proved to be associated with BAE. Only five patients (5.5%) underwent cholecystectomy for symptomatic cholelithiasis. 71% of patients started UDCA treatment, achieving regression of BAE in 60% of cases (88% in patients developing only sludge and 30% in patients affected by cholelithiasis, p < 0.001). BMI and obesity were negative predictors of UDCA efficacy. In 50% of the subjects BAE resolved after 36 months of therapy with a lower rate if cholelithiasis was present. CONCLUSION: Biliary stone disease is a frequent SRL adverse event, although it is often symptomless. Ultrasound follow-up mainly in the first 5 years of therapy, early UDCA starting and proper lifestyle represent a valid strategy in their detection and management.

The Induction of Antioxidant Catalase Enzyme With Decrease of Plasma Malonidialdehyde: An Important Reactive Oxidative Species Inhibiting Mechanism.

BACKGROUND/AIM: The simultaneous increase of antioxidant CAT (catalase) enzyme and plasma MDA (malonidialdehyde) concentrations versus the numeric rating scale (NRS) pain score following surgery is unknown. Patients and Methods: The study included 114 patients with gallstone disease and 29 patients in the cancer group. RESULTS: Following surgery, the plasma CAT concentrations increased and plasma MDA concentrations decreased in all patients and especially in cancer patients. The linear mixed model time-effect was statistically significant in CAT and MDA (p<0.001 and p=0.02, respectively). In addition, a significant correlation between NRS pain score values and plasma MDA median concentrations in cancer patients was identified (r=0.430, p<0.001). CONCLUSION: The plasma MDA concentrations decreased and CAT concentrations increased significantly in all patients and especially in cancer patients following surgery. The simultaneous increase of antioxidant CAT enzyme with the decrease of plasma MDA may be an important ROS inhibiting mechanism to help patients return to normal antioxidant-oxidant status.

Physical activity can reduce the prevalence of gallstone disease among males: An observational study.

Several previous studies have reported that physical activity (PA) levels can independently affect the prevalence of gallstone disease (GD) in Western countries. However, this association has not been reported in Eastern countries. Therefore, this study aimed to determine whether PA is an independent determinant of GD prevalence in a Korean population, according to the World Health Organizations Global Recommendations on PA for Health.A total of 8908 subjects who completed a questionnaire underwent medical examination and ultrasound scanning at the Health Promotion Center of the Jeju National University Hospital between January 2009 and December 2018. GD and fatty liver disease were diagnosed by abdominal ultrasound. Biochemical parameters and body mass index were determined, and metabolic syndrome status, age, and PA levels were extracted from medical records. Univariate and multivariate analyses were performed to identify independent factors affecting GD.The estimated rates of PA and GD among male subjects were 23.7% and 4.6%, whereas the rates among females were 18.4% and 4.2%, respectively. Multivariate analysis suggested that no PA, old age, and higher aspartate aminotransferase level in males and nonalcoholic fatty liver disease status in females were independent factors affecting GD.In our study, PA was associated with a reduction in GD among males but not females.

Normalization of Serum Lipase Levels Versus Resolution of Abdominal Pain: A Comparison of Preoperative Management in Children With Biliary Pancreatitis.

BACKGROUND: Controversy exists over the timing of cholecystectomy for biliary pancreatitis in children. Some surgeons await normalization of serum lipase levels while others are guided by resolution of abdominal pain; however, there are minimal data to support either practice. We hypothesized that resolution of abdominal pain is equivalent in outcome to awaiting normalization of lipase levels in patients undergoing cholecystectomy for biliary pancreatitis. METHODS: After institutional review board (IRB) approval, the medical record was retrospectively queried for all cases of cholecystectomy for biliary pancreatitis at our institution from 2007 to 2017. Patients undergoing chemotherapy, admitted for another cause, or who had severe underlying comorbidities like ventilator dependence were excluded. Patients were stratified into two cohorts: those managed preoperatively by normalization of serum lipase levels versus resolution of abdominal pain. Demographics, serum lipase levels, postoperative complications, cost of stay, readmissions, and return to the emergency department were collected and analyzed using multivariate regression. RESULTS: Seventy-four patients met inclusion: 29 patients had lipase levels trended until normalization compared with 45 patients who had resolution of abdominal pain prior to cholecystectomy. Among the two cohorts there was no statistical difference in age, gender, race, ethnicity, or type of preoperative imaging used. Trended patients were found to have more serum lipase levels tested (8.5 ± 6.2 versus 3.4 ± 2.5, P < 0.0001). The trended lipase cohort was significantly more likely to require preoperative total parenteral nutrition (48% versus 11%, P = 0.007) and consequently a longer time before resuming a diet (10 ± 7.3 versus 4.6 ± 2.4 d, P < 0.0001). When comparing the two groups, we found no significant difference in the duration of surgery, postoperative complications, or readmissions. Lipase trended patients had a significantly longer length of stay compared with nontrended patients (11.5 ± 8.1 versus 4.2 ± 2.3 d, P < 0.0001) and had a higher total cost of stay ($38,094 ± 25,910 versus $20,205 ± 5918, P = 0.0007). CONCLUSIONS: Our data suggest that in children with biliary pancreatitis, proceeding with cholecystectomy after resolution of abdominal pain is equivalent in outcomes to trending serum lipase levels but is more cost-effective with a decreased length of stay and decreased need for preoperative total parenteral nutrition.

Serum lipid levels are the risk factors of gallbladder stones: a population-based study in China.

BACKGROUND: Gallstones are the cause of a majority of biliary tract discomfort. Although many community-based studies have addressed the risk factors for gallstone disease (GSD), little is known about GSD prevalence and risk factors in Chinese populations. METHODS: From January 2014 to January 2015, participants (N = 2,068,523) were recruited by Meinian Onehealth Healthcare Co., Ltd. They received a physical examination, and GSD was determined by ultrasound. RESULTS: The prevalence of GSD was 8.1%. Risks of GSD were similar between males and females in all age groups. Risk factors for gallstones include body mass index, waist circumference, waist-to-hip ratio, and physical activity, as well as biological factors such as age, sex, and elevated blood lipid levels. Serum lipid levels of GSD were statistically different from controls in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (H-DL), low-density lipoprotein cholesterol (LDL), and apolipoprotein B (APOB). Furthermore, TC > 5.00 mmol/L, TG > 1.39 mmol/L, HDL < 1.19 mmol/L, LDL > 3.04 mmol/L, and APOB > 0.97 mmol/L were risk factors for gallstones. CONCLUSIONS: Serum lipid levels are associated with GSD. TC, TG, LDL, and APOB are risk factors, while HDL is a protective factor.

A Metallomic Approach to Assess Associations of Serum Metal Levels With Gallstones and Gallbladder Cancer.

BACKGROUND AND AIMS: Exposure to metals may promote the risk for cancers. We evaluated the associations of a broad spectrum of metals with gallbladder cancer (GBC) and gallstones. APPROACH AND RESULTS: A total of 259 patients with GBC, 701 patients with gallstones, and 851 population-based controls were enrolled in Shanghai, China. A metallome panel was used to simultaneously detect 18 metals in serum through inductively coupled plasma-mass spectrometry. Logistic regression models were used to estimate crude or adjusted odds ratios (ORadj ) with 95% confidence intervals (CIs) for the association between metal levels and gallbladder disease. Among the 18 metals tested, 12 were significantly associated with GBC and six with gallstones (Pcorrected  < 0.002). Boron, lithium, molybdenum, and arsenic levels were associated with GBC compared to gallstones as well as with gallstones compared to population-based controls. Elevated levels of cadmium, chromium, copper, molybdenum, and vanadium were positively associated with GBC versus gallstones; and the ORadj for the highest tertile (T3) compared to the lowest tertile (T1) ranged from 1.80 to 7.28, with evidence of dose-response trends (P < 0.05). Arsenic, boron, iron, lithium, magnesium, selenium, and sulfur were inversely associated with GBC, with the T3 versus T1 ORadj ranging from 0.20 to 0.69. Arsenic, boron, calcium, lithium, molybdenum, and phosphorus were negatively associated with gallstones, with the T3 versus T1 ORadj ranging from 0.50 to 0.75 (P < 0.05). CONCLUSIONS: Metals were associated with both GBC and gallstones, providing cross-sectional evidence of association across the natural history of disease. Longitudinal studies are needed to evaluate the temporality of metal exposure and gallbladder diseases and to investigate the mechanisms of disease pathogenesis.

Microstructural diversity of gallstones revealed by spectral microanalyses and their association with hepatic parameters.

BACKGROUND: Gallstones (GS) are formed as a result of impaired metabolic regulation and can be reflected in serum parameters. This study was focused on classifying GS based on spectral microanalysis and identifying the possible role of serum hepatic parameters on GS of different compositions. METHODS: The study included a total of 126 GS from 80 consecutive patients who underwent cholecystectomy for GS diseases in a single center. The composition and microstructure of GS were analyzed using Fourier-transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), and energy dispersive X-ray spectroscopy (EDS). The serum hepatic parameters were studied in order to establish a possible etiologic relationship with GS composition. RESULTS: In the study group, the incidence of GS was higher in females 62 (77.5%) compared with males 18 (22.5%). The mean age was 42.81 ± 13.01 and 43.78 ± 14.4 years for female and male patients, respectively. Based on composition, the GS were assigned to four major groups: cholesterol, pigment, phosphate, and mixed stones. Mixed composition stones totally represented the majority 53 (66.3%), followed by pure cholesterol 23 (28.8%), pigment stones 2 (2.5%), and phosphate stones 2 (2.5%), respectively. Elemental composition revealed the presence of carbon (C), oxygen (O), calcium (Ca), and phosphorus (P) to be major elements along with traces of sodium (Na), magnesium (Mg), aluminum (Al), iron (Fe), copper (Cu), bromine (Br), manganese (Mn), and zinc (Zn). Among serum parameters, total bilirubin, direct bilirubin, indirect bilirubin, serum glutamic-oxaloacetic transaminase, and total protein were higher in patients with pigment GS than cholesterol GS. CONCLUSIONS: Characterization of GS indicates that different types of stones have different characteristics in terms of microstructure, elemental composition, and distribution. Serum hepatic function test profiles showed an association with the compositions of GS.

Screening of Sera from Patients with Pancreatitis by an Apoptosis Assay of Skin-derived Cells.

BACKGROUND/AIMS: An excessive inflammatory response is typical in acute pancreatitis and a significant cause of early mortality in severe acute pancreatitis. This is believed to be caused by inflammatory molecules or upregulated cytokine levels in the serum of patients. The aim of this study was to identify the serum-mediated apoptosis-inducing effects in acute pancreatitis patients. METHODS: A skin tissue-derived cell line, BJ, was treated for 24 hours with the sera of 22 healthy volunteers (control) and 71 acute pancreatitis patients (22 with gallstone pancreatitis, 16 with alcoholic pancreatitis, and 11 with pancreatitis with other causes) collected at the time of hospital admission (active) and discharge (resolved). Apoptosis was analyzed by flow cytometry. RESULTS: The average percentage of living cells, early apoptotic cells, and late apoptotic cells ranged from 78.8% to 85.0%, 5.5% to 7.3%, and 7.7% to 13.1%, respectively. The number of live cells increased significantly using the serum from the resolved state of gallstone-induced pancreatitis. In addition, the number of early apoptotic cells increased significantly using the serum from the resolved state of pancreatitis with other causes. The number of late apoptotic cells decreased significantly with the serum from the resolved state compared to the active state of gallstone- and alcohol-induced pancreatitis. CONCLUSIONS: Serum samples from patients with pancreatitis induced a change in the apoptosis profiles of skin-derived cells. These results indicate changes in the serum components in patients with acute pancreatitis.

Obeticholic acid may increase the risk of gallstone formation in susceptible patients.

BACKGROUND & AIMS: The nuclear farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has been developed for the treatment of liver diseases. We aimed to determine whether OCA treatment increases the risk of gallstone formation. METHODS: Twenty patients awaiting laparoscopic cholecystectomy were randomized to treatment with OCA (25 mg/day) or placebo for 3 weeks until the day before surgery. Serum bile acids (BAs), the BA synthesis marker C4 (7α-hydroxy-4-cholesten-3-one), and fibroblast growth factor 19 (FGF19) were measured before and after treatment. During surgery, biopsies from the liver and the whole bile-filled gallbladder were collected for analyses of gene expression, biliary lipids and FGF19. RESULTS: In serum, OCA increased FGF19 (from 95.0 ±â€¯8.5 to 234.4 ±â€¯35.6 ng/L) and decreased C4 (from 31.4 ±â€¯22.8 to 2.8 ±â€¯4.0 nmol/L) and endogenous BAs (from 1,312.2 ±â€¯236.2 to 517.7 ±â€¯178.9 nmol/L; all p <0.05). At surgery, BAs in gallbladder bile were lower in patients that received OCA than in controls (OCA, 77.9 ±â€¯53.6 mmol/L; placebo, 196.4 ±â€¯99.3 mmol/L; p <0.01), resulting in a higher cholesterol saturation index (OCA, 2.8 ±â€¯1.1; placebo, 1.8 ±â€¯0.8; p <0.05). In addition, hydrophobic OCA conjugates accounted for 13.6 ±â€¯5.0% of gallbladder BAs after OCA treatment, resulting in a higher hydrophobicity index (OCA, 0.43 ±â€¯0.09; placebo, 0.34 ±â€¯0.07, p <0.05). Gallbladder FGF19 levels were 3-fold higher in OCA patients than in controls (OCA, 40.3 ±â€¯16.5 ng/L; placebo, 13.5 ±â€¯13.1 ng/ml; p <0.005). Gene expression analysis indicated that FGF19 mainly originated from the gallbladder epithelium. CONCLUSIONS: Our results show for the first time an enrichment of FGF19 in human bile after OCA treatment. In accordance with its murine homolog FGF15, FGF19 might trigger relaxation and filling of the gallbladder which, in combination with increased cholesterol saturation and BA hydrophobicity, would enhance the risk of gallstone development. LAY SUMMARY: Obeticholic acid increased human gallbladder cholesterol saturation and bile acid hydrophobicity, both decreasing cholesterol solubility in bile. Together with increased hepatobiliary levels of fibroblast growth factor 19, our findings suggest that pharmacological activation of the farnesoid X receptor increases the risk of gallstone formation. Clinical trial number: NCT01625026.

Altered Bile Transporter Expression and Cholesterol Metabolism in Children With Cholesterol and Pigment Gallstones.

OBJECTIVES: We elucidated pathophysiology of pediatric gallstone disease by assessing liver expression of bile transporters in relation to bile acids and surrogates of cholesterol absorption and synthesis in serum and gallstones. METHODS: RNA expression of canalicular bile transporters in liver biopsies from 32 pediatric gallstone patients and from 6 liver donors (controls) was measured by qRT-PCR (quantitative real-time reverse transcription polymerase chain reaction). Concentrations of cholesterol and precursors, plant sterols and bile acids in gallstones, and in serum of the patients and 82 healthy children were measured. Primary outcomes were the difference in RNA expressions and serum sterol profiles between patients and controls. RESULTS: Cholesterol stones (CS; n = 15) contained cholesterol >42% and pigment stones (PS; n = 17) <9% of weight. CS patients had markedly lower serum plant sterols (absorption) and higher cholesterol precursors (synthesis) than PS patients or healthy controls. CS contained several times more cholesterol precursors and less plant sterols relative to cholesterol than PS, which were enriched by primary bile acids (12-5.2-fold, P < 0.001). Liver RNA expression of ABCG5/G8 was similarly increased 2.5- to 1.8-fold (P < 0.002) in CS and PS patients, whereas PS patients had higher ABCB11 expression (P < 0.05). In PS bile acid concentration correlated with gallstone plant sterols (R = 0.83, P < 0.0001), and ABCG5 expression with ABCB11 expression (R = 0.27, P = 0.03). CONCLUSIONS: In CS, upregulation of ABCG5/G8 expression associates with low absorption and high gallstone content of cholesterol. In PS, activation of bile acid transport by ACBC11 interconnects with hepatic upregulation of ABCG5/G8 enriching PS with bile acids and plant sterols.

Molecular diagnostic update in hereditary hemolytic anemia and neonatal hyperbilirubinemia.

Hereditary hemolytic anemia (HHA) is a group of genetically and phenotypically heterogeneous disorders characterized by premature destruction of red blood cells (RBCs) with clinical manifestations ranging from asymptomatic to marked hemolytic anemia. There are three main categories of HHA: (a) RBC membrane defects; (b) hemoglobinopathies/thalassemias; and (c) RBC enzyme deficiencies. Hyperbilirubinemia is a frequent consequence of hemolytic anemia and can lead to bilirubin-associated neurotoxicity in neonates and to jaundice, and formation of gall stones in adults. Hyperbilirubinemia can also be caused by impaired bilirubin conjugation due to polymorphisms and mutations in genes involved in bilirubin metabolism (eg, UGT1A1). Neonates with HHA and co-inherited variants impairing bilirubin conjugation are at increased risk of bilirubin-associated toxicity. Prior to the advent of next-generation sequencing (NGS), molecular diagnosis of these disorders was limited to targeted single gene Sanger sequencing. However, NGS is making its way into the standard diagnostic workup of complex and multigene disorders like HHA. This review will focus on the molecular updates of HHA with particular focus on the neonatal and pediatric population.

Adiponectin accounts for gender differences in hepatocellular carcinoma incidence.

Hepatocellular carcinoma (HCC) is the sixth most common cancer type and the fourth leading cause of cancer-related death. This cancer appears with higher incidence in men and during obesity; however, the specific mechanisms underlying this correlation are unknown. Adipose tissue, a key organ in metabolic syndrome, shows evident gender disparities in the production of adipokines. Levels of the important adipokine adiponectin decrease in men during puberty, as well as in the obese state. Here, we show that this decrease in adiponectin levels is responsible for the increased liver cancer risk in males. We found that testosterone activates the protein JNK in mouse and human adipocytes. JNK-mediated inhibition of adiponectin secretion increases liver cancer cell proliferation, since adiponectin protects against liver cancer development through the activation of AMP-activated protein kinase (AMPK) and p38α. This study provides insight into adipose tissue to liver crosstalk and its gender relation during cancer development, having the potential to guide strategies for new cancer therapeutics.

Nitrotyrosine (NT), a Nitrosative Stress Biomarker, Plasma Concentrations in Gallstone Disease and Cancer Patients.

BACKGROUND/AIM: The aim of this study was to assess the plasma concentration of the nitrosative stress biomarker nitrotyrosine (NT) in gallstone disease and cancer patients. MATERIALS AND METHODS: Initially, 114 patients with symptomatic gallstone disease were randomized into the laparoscopic cholecystectomy (LC) (n=54) and the minicholecystectomy (MC) (n=60) groups. The plasma concentrations of NT were measured just before, immediately after (POP1) and 6 h after operation (POP2). The cancer patients of this study included ten patients with gastrointestinal cancer and 19 patients with gynecological cancer. RESULTS: There was a statistically significant correlation in the median plasma NT concentrations versus plasma catalase (CAT) concentrations in cholecystectomy patients (r=0.169, p=0.001). Interestingly, there was a statistically significant inverse correlation between the individual values of the pain assessed and filed using a 11-point numeric rating scale 8 h postoperatively (NAD8) and plasma NT median values in cholecystectomy patients (r=-0.337, p=0.004). CONCLUSION: Patients with high plasma concentrations of NT appeared to have significantly lower pain scores 8 h postoperatively.

Identification and Replication of Six Loci Associated With Gallstone Disease.

Gallstone disease is a common complex disease that confers a substantial economic burden on society. The genetic underpinnings of gallstone disease remain incompletely understood. We aimed to identify genetic associations with gallstone disease using publicly available data from the UK Biobank and two large Danish cohorts. We extracted genetic associations with gallstone disease from the Global Biobank Engine (GBE), an online browser of genome-wide associations in UK Biobank participants (14,940 cases and 322,268 controls). Significant associations (P < 5 × 10-8 ) were retested in two Copenhagen cohorts (comprising 1,522 cases and 18,266 controls). In the Copenhagen cohorts, we also tested whether a genetic risk score was associated with gallstone disease and whether individual gallstone loci were associated with plasma levels of lipids, lipoproteins, and liver enzymes. We identified 19 loci to be associated with gallstone disease in the GBE. Of these, 12 were replicated in the Copenhagen cohorts, including six previously unknown loci (in hepatocyte nuclear factor 4 alpha [HNF4A], fucosyltransferase 2, serpin family A member 1 [SERPINA1], jumonji domain containing 1C, AC074212.3, and solute carrier family 10A member 2 [SLC10A2]) and six known loci (in adenosine triphosphate binding cassette subfamily G member 8 [ABCG8], sulfotransferase family 2A member 1, cytochrome P450 7A1, transmembrane 4 L six family member 4, ABCB4, and tetratricopeptide repeat domain 39B). Five of the gallstone associations are protein-altering variants, and three (HNF4A p.Thr139Ile, SERPINA1 p.Glu366Lys, and SLC10A2 p.Pro290Ser) conferred per-allele odds ratios for gallstone disease of 1.30-1.36. Individuals with a genetic risk score >2.5 (prevalence 1%) had a 5-fold increased risk of gallstones compared to those with a score <1.0 (11%). Of the 19 lithogenic loci, 11 and ten exhibited distinct patterns of association with plasma levels of lipids and liver enzymes, respectively. Conclusion: We identified six susceptibility loci for gallstone disease.

Total bilirubin trend as a predictor of common bile duct stones in acute cholecystitis and symptomatic cholelithiasis.

BACKGROUND: We hypothesized that trends in total bilirubin in the context of cholecystitis and symptomatic cholelithiasis could be used to guide testing for the presence of common bile duct stones (CBDS). METHODS: A review of adult patients with acute cholecystitis or biliary colic with elevated total bilirubin and at least two levels drawn prior to procedural intervention was performed. Trends of total bilirubin and other serum makers were examined to predict the presence of CBDS. RESULTS: The total bilirubin level at presentation, average over 24 h and average over 48 h (3.74 mg/dl vs. 2.29 mg/dl, p = 0.005; 3.72 mg/dl vs. 2.40 mg/dl, p = 0.009; 2.41 mg/dl vs. 1.47 mg/dl, p < 0.001) respectively, were all higher in those with CBDS. However, prediction was not improved by following levels over time. CONCLUSION: Patients presenting with elevated serum bilirubin, should undergo immediate imaging or procedural intervention rather than obtaining follow-up bilirubin levels.

Fast Morphological Gallbladder Changes Triggered by a Hypercholesterolemic Diet.

INTRODUCTION AND AIM: Obesity is a worldwide epidemic problem, described as a risk factor for hepatic diseases, such as non-alcoholic fatty liver disease and other pathologies related to development of cholesterol crystals and cholesterol gallbladder stones. It has been reported that cholesterol overload may cause hepatic damage; however, little is known about the effects of an acute hypercholesterolemic diet on the gallbladder. The aim of this manuscript was to evaluate the impact of a cholesterol-rich diet on the gallbladder. MATERIAL AND METHODS: The study included ten eight-week-old C57BL6 male mice, which were divided into two study groups and fed different diets for 48 h: a hypercholesterolemic diet and a balanced Chow diet. After 48 h, the mice were analyzed by US with a Siemens Acuson Antares equipment. Mice were subsequently sacrificed to carry out a cholesterol analysis with a Refloton System (Roche), a crystal analysis with a Carl Zeiss microscope with polarized light, and a histological analysis with Hematoxylin-eosin staining. RESULTS: The hypercholesterolemic diet induced an increase in gallbladder size and total cholesterol content in the bile, along with important histological changes. CONCLUSION: Cholesterol overloads not only trigger hepatic damage, but also affect the gallbladder significantly.

Plasma Helicobacter pylori Antibody Titers and Helicobacter pylori Infection Positivity Rates in Patients with Gallbladder Cancer or Cholelithiasis: a Hospital-Based Case-Control Study

Objective: Gallbladder cancer is the commonest gastrointestinal cancer in northern Indian women. Some studies have examined the association between Helicobacter pylori infection and gallbladder cancer risk, but findings have been inconsistent. We aimed to examine the association between H. pylori infection and gallbladder cancer in Indian people. Materials and Methods: We conducted a hospital-based case-control study including 100 gallbladder cancer patients with gallstones who were 32 to 79 years old (cases; 72 women and 28 men), and 100 cholelithiasis patients aged 14 to 75 years (controls; 65 women and 35 men). All patients had a diagnosis of gallbladder cancer or cholelithiasis at the Sanjay Gandhi Post Graduate Institute of Medical Sciences in Lucknow having a high gallbladder cancer incidence in northern India, from May 2014 through July 2017. Plasma samples were collected from all patients before surgical treatment. Plasma H. pylori antibody titer was measured by the latex agglutination method and an autoanalyzer. H. pylori infection was defined as antibody titer ≥10 U/mL. Plasma antibody titers and H. pylori infection positivity rates were compared between cases and controls. Results: Mean plasma antibody titers (standard deviation, range) were 11.1 U/mL (11.6, 0­78) in cases and 13.6 U/mL (23.0, 1­164) in controls. H. pylori infection positivity rates were 41% and 42% in cases and controls, respectively. No significant differences in antibody titers or H. pylori infection positivity rates were found between cases and controls. Conclusions: We found no evidence of H. pylori infection as an important risk factor for gallbladder cancer in Indian people.

Genetic polymorphism of sterol transporters in children with future gallstones.

BACKGROUND & AIMS: Gallstone disease is related to hypersecretion of cholesterol in bile, and low serum phytosterol levels. We examined how genetic polymorphisms of sterol transporters affect childhood cholesterol metabolism trait predicting adult gallstone disease. PATIENTS AND METHODS: In retrospective controlled study, we determined D19H polymorphism of ABCG8 gene, genetic variation at Niemann-Pick C1-like 1 (NPC1L1) gene locus (rs41279633, rs17655652, rs2072183, rs217434 and rs2073548), and serum cholesterol, noncholesterol sterols and lipids in children affected by gallstones decades later (n = 66) and controls (n = 126). RESULTS: In childhood, phytosterols were lower (9.7%-23.4%) in carriers of risk allele 19H compared to 19D homozygotes. Lowest campesterol/cholesterol tertile consisted of 1.9-times more future gallstone subjects, and 3.7-times more 19H carriers than highest one. Campesterol/cholesterol-ratio was highest in 19D homozygote controls, but ∼11% lower in gallstone 19D homozygotes and ∼25% lower among gallstone and control carriers of 19H. Gallstone subjects with alleles CC of rs41279633 and TT of rs217434 of NPC1L1 had ∼18% lower campesterol/cholesterol-ratio compared to mutation carriers. CONCLUSIONS: Risk trait of cholesterol metabolism (low phytosterols) in childhood favouring cholesterol gallstone disease later in adulthood is influenced by risk variant 19H of ABCG8 and obviously also other factors. NPC1L1 variants have minor influence on noncholesterol sterols.

Fluctuating Pulse Oximetry Readings in an Adolescent With Hemoglobin Bibba: A Case Report.

Hemoglobinopathies caused by unstable hemoglobins represent a wide group of diseases that include hemoglobin Bibba. Hemoglobin instability may cause chronic hemolytic anemia and conformational changes in hemoglobin that affect affinity for oxygen and absorption of wavelengths of light used in pulse oximetry devices. We report the case of an adolescent with hemoglobin Bibba and α-thalassemia. SpO2 was unexpectedly low despite stable vital signs when his hemoglobin was closer to 10 g/dL and normal when his hemoglobin was lower, presumably when there was less unstable hemoglobin because of hemolysis.