Our survey reveals a consistent approach in line with the more re

Our survey reveals a consistent approach in line with the more recent studies.

There are few published data on the optimal management of less common joint bleeds such as hips and shoulders. As illustrated by the literature review, there is little evidence-based information to determine the role of diagnostic procedures (radiological examination, arthroscopy) or adjunctive therapies (aspiration, pain control, physiotherapy, cooling measures, anti-inflammatory agents and embolization) in the management of acute haemarthrosis and our survey shows significant heterogeneity in approach. This lack of evidence is again well reflected in current guidelines, which do not provide standardized and detailed protocols of adjunctive therapies. Such information appears, however, critical INCB024360 research buy in view of recent insights into the pathophysiology of haemophilic arthropathy and the understanding of the blood toxicity. Although non-weight bearing appears to be an important adjunctive measure in all patients, the role of joint aspiration to preserve joint function in patients with major haemarthrosis remains to be clarified. This survey, conducted among a large group of treaters caring for several thousand haemophilia patients, provides interesting information on treatment practices, including target factor levels, duration

of treatment and use of certain treatment modalities. The survey highlights much heterogeneity in the management of acute haemarthrosis across the MG-132 chemical structure EU. The prescribed treatment regimens were usually more intensive, targeting higher factor levels, than those reported in the literature and current guidelines. Only a minority of the treaters considered joint aspiration to be a useful adjunctive treatment.

Because of the limitations of the literature, it is not possible to provide evidence-based guidelines for the optimal management of acute haemarthrosis in patients with Thiamet G haemophilia. However, based on the results of literature review, survey and discussion within the EHTSB, consensus was reached on the following recommendations [the level of evidence (see Table 5) is shown in parenthesis]: Replacement therapy.  Recent studies and clinical consensus quote and support initial treatment with 25–40 IU kg−1 FVIII concentrate. In the vast majority of cases, this will resolve with one treatment [26–29]. Higher doses such as 50 IU kg−1 may be necessary for more severe bleeds e.g. post-traumatic. Replacement therapy should be initiated as soon as possible and repeated until satisfactory resolution defined as resolution of pain and recovery of function (grade B, level III). Acute analgesia and anti-inflammatory agents.  Immobilization and the use of ice may be helpful in the relief of pain and to resolve the bleed.

11) the odds of bleeding events (grades 3-5) as compared to a non

11) the odds of bleeding events (grades 3-5) as compared to a non-antiangiogenic control. To examine the risk of bleeding event in antiangiogenic therapy compared to non-antiangiogenic therapy among single-arm studies in HCC, 19 studies incorporating antiangiogenic therapy and 21 with non-antiangiogenic therapy (Tables 2, 3) were analyzed. Figure 2 shows that, among single-arm HCC studies, the OR for any bleeding event with antiangiogenic therapy is 4.34 (2.16, 8.73; P < 0.0001). The selleck inhibitor OR of bleeding

event grades 3-5 for antiangiogenic therapy are 2.66 (95% CI 1.03, 6.82; P = 0.0425). This suggests that antiangiogenic therapy significantly increases the odds of bleeding events (both all grades and grades 3-5) as compared to non-antiangiogenic therapy in single-arm HCC studies. In order to determine if the observed trend towards increased hemorrhagic risk was inherent to HCC or was a class effect, we examined the effect of sorafenib on bleeding events in RCC (Fig. 3). Among the RCC randomized studies, treatment with sorafenib significantly increased the odds of any bleeding event (OR 1.92; 95% CI 1.30, 2.85) compared to control. The test for subgroup differences showed the effect of sorafenib

on any bleeding event to be similar between the HCC and RCC subgroups (P = 0.75). Similar to the HCC result, treatment with sorafenib Y-27632 price did not significantly increase the odds of bleeding events grades 3-5 (OR 1.18; 95% CI 0.58 to 2.38) among the RCC randomized studies. The overall pooled Cell press estimate of HCC and RCC studies also indicates a nonsignificant effect of sorafenib on bleeding events grades 3-5 (OR

1.43; 95% CI 0.88, 2.32), which was similar for both HCC and RCC subgroups (P = 0.45). Worldwide, HCC is the fifth most common malignancy, with a median survival of 6-9 months.5 In the United States the incidence of HCC continues to rise, a trend which will likely result in more clinical trials being performed in this disease.6, 7 In addition, after decades of negative studies in HCC the SHARP and AP studies provided an impetus for the investigation of “antiangiogenic” strategies in HCC in an effort to bolster the relatively small gains made with sorafenib. We have learned however from the experience in other tumor types that anti-vascular endothelial growth factor (VEGF) therapies are associated with class toxicities, including bleeding. In one meta-analysis of bevacizumab-related toxicities, hemorrhagic events accounted for almost one-quarter of the fatal adverse events seen.8 In HCC this is a particular concern because of the almost invariable presence of cirrhosis in this patient population, placing them at an elevated baseline risk of hemorrhage. The main purpose of this analysis was to determine if there was an increased risk of bleeding for a patient with HCC taking part in a study evaluating an antiangiogenic therapy.

This study attempted to assess whether polymorphisms in the lepti

This study attempted to assess whether polymorphisms in the leptin receptor (LEPR) gene and its combined effect with patatin-like phospholipase domain-containing protein Napabucasin in vivo 3 (PNPLA3/adiponutrin) are associated with risk of NAFLD. A total of 144 biopsy-proven NAFLD and 198 controls were genotyped using the Sequenom MassARRAY platform. We observed a significant association between the LEPR rs1137100 and rs1137101 with susceptibility to NAFLD (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.18–2.28, P = 0.003; and OR 1.61, 95% CI 1.11–2.34, P = 0.013, respectively) and to non-alcoholic steatohepatitis

(OR 1.49, 95% CI 1.05–2.12, P = 0.026; and OR 1.57, 95% CI 1.05–2.35, P = 0.029, respectively). The LEPR rs1137100 is also associated with simple steatosis (OR 2.27, 95% CI 1.27–4.08, P = 0.006). Analysis of gene–gene interaction revealed a strong interaction between the LEPR and PNPLA3 genes (empirical P = 0.001). Forskolin The joint effect of LEPR and PNPLA3 greatly exacerbated the risk of NAFLD (OR 3.73, 95% CI 1.84–7.55, P < 0.0001). The G allele of rs1137100 is associated with lower fibrosis score (OR 0.47, 95% CI 0.28–0.78, P = 0.001). We report an association between variants of LEPR rs1137100 and rs1137101 with risk of NAFLD. This

study suggests that rs1137100, specifically the G allele, is associated with a less severe form of liver disease in patients with NAFLD. The interaction between LEPR and PNPLA3 genes showed increased risk of NAFLD Niclosamide compared to either gene alone. “
“Chaetocin, an antibiotic produced by Chaetomium species fungi, was recently found to have antimyeloma activity. Here we examined whether chaetocin has

anticancer activities against solid tumors. Chaetocin inhibited the growth of mouse and human hepatoma grafts in nude mice. Immunohistochemical analyses revealed that chaetocin inhibits hypoxia-inducible factor-1α (HIF-1α) expression and vessel formation in the tumors. Chaetocin also showed antiangiogenic anticancer activities in HIF-1α(+/+) fibrosarcoma grafted in mice, but not in HIF-1α(−/−) fibrosarcoma. Biochemical analyses showed that chaetocin down-regulated HIF-1α and the transcripts of HIF-1 target genes including vascular endothelial growth factor in hepatoma tissues and in various hepatoma cell lines. Based on the reported literature, unsuccessful efforts were made to determine the mechanism underlying the action of chaetocin. Unexpectedly, chaetocin was found to cause the accumulation of HIF-1α premessenger RNA (pre-mRNA) but to reduce mature mRNA levels in hepatoma cells and tissues. Such an effect of chaetocin was not observed in cell lines derived from normal cells, and was cell type-dependent even among cancer cell lines. Conclusions: Our results suggest that chaetocin could be developed as an anticancer agent to target HIF-1 in some cancers including hepatoma.

The cause of PGCH is unknown and probably multifactorial; possibi

The cause of PGCH is unknown and probably multifactorial; possibilities include a virus,8,

9 drugs and herbal remedies,10 and autoimmune changes.11, 12 In addition, reports have been published about patients who have undergone liver transplantation.13, 14 Our patient received Pil-Food. Severe changes in liver function tests occurred, she was positive for antinuclear antibody autoreactivity, and a histological examination found abundant PF-01367338 nmr areas of multinucleate giant cells with marked periportal and parenchymal hepatocellular necrosis and inflammation. Because all the aforementioned alterations appeared during the long-term ingestion of Pil-Food [a composition developed by Synthelabo that contains D,L-methionine, GDC-0068 cost L-(+)-cysteine hydrochloride, L-cysteine, enzymes and animal protein hydrolysates, millet extract, calcium pantothenate, vitamin B2 phosphate, vitamin B6, biotin (vitamin H), and vitamin E] and a successful corticosteroid response was attained, we speculate that this hepatic autoreactivity could be related to the Pil-Food treatment.15, 16 Moreover, just like patients with drug-induced AIH,1 our patient did not require long-term immunosuppressive therapy. We believe that this case highlights (1) that the breakdown of immune tolerance by drugs is able to trigger liver autoreactivity and (2) that some cases of PGCH may present a rapid and effective response

to corticosteroid therapy instead of a fulminant or progressive course. Ricardo Moreno-Otero M.D.* ‡, Maria Trapero Marugán M.D.* ‡, Luisa García-Buey M.D.* ‡, Asunción García-Sancchez Adenosine M.D.†, * Digestive Diseases Service, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid, Madrid, Spain, † Pathology Service, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid,

Madrid, Spain, ‡ Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Madrid, Spain. “
“A 53 year-old man presented with a 5-month history of severe diarrhoea and abdominal cramping immediately occurring after tube feeding. The Percutaneous Endoscopic Gastrostomy (PEG) tube was inserted 2 years previously, for enteral feeding, following diagnosis of an oropharyngeal carcinoma. The patient had no signs or symptoms of peritonitis. The skin surrounding the tube was inflamed with brown odorous fluid exuding. Upon checking the tube position using upper endoscopy no inner bumper was seen within the stomach. A fistulogram through the feeding tube revealed typical haustration of the colon rather than expected gastric appearances (Figure 1A). CT confirmed misplacement, localizing the position of the bumper in the transverse colon (Figure 1B, arrow). A gastrocolic fistula could not be visualized. Colonoscopy showed the inner bumper located near the splenic flexure (Figure 2A).

siRNA was prepared by Qiagen (HP GenomeWide siRNA, Qiagen, Hilden

siRNA was prepared by Qiagen (HP GenomeWide siRNA, Qiagen, Hilden, Germany) targeting the β1 integrin sequence 5′-AAA AGT CTT GGA ACA GAT CTG-3′. Cells were washed three times with serum-free Dulbecco’s modified Eagle’s medium Nutrimix F12 + 0,5% geneticin followed

by siRNA transfection using HiPerFect transfection reagent (Qiagen) according selleck inhibitor to the manufacturer’s instruction. Results from at least three independent experiments are expressed as means ± SEM (standard error of the mean). Results were analyzed using Student’s t test: P < 0.05 was considered statistically significant. A detailed description of how starting structures for MD simulations of α5β1 integrin bound to either TUDC, TC, or GRGDSP were generated and how MD simulations of in total 1.050 μs length of these systems were performed and analyzed is provided in the Supporting Text. Integrin sequence numbers are according

to Uniprot. In isolated perfused rat liver, addition of TUDC at a concentration of 20 μmol/L induced within 1 minute the appearance of the active conformation of β1 integrin, whereas in the absence of TUDC the active β1-isoform was only scarcely detectable (Fig. 1A; see Supporting Fig. 1 for total α5β1 integrin staining). TUDC-induced β1 integrin activation was predominantly observed inside the hepatocytes (Fig. 1B). Equimolar concentrations of other bile acids, such as taurocholic acid (TC), glycochenodeoxycholic acid (GCDC), taurochenodeoxycholic acid (TCDC), or tauro-lithocholic acid 3-sulfate (TLCS) were

ineffective with regard to β1 integrin activation (Supporting Fig. 2). Rho https://www.selleckchem.com/products/VX-770.html None of the bile acids had any effect on the immunostaining for total α5β1 integrins (Supporting Fig. 3). TUDC-induced integrin activation was sensitive to inhibition by the RGD-motif containing hexapeptide GRGDSP, which also prevented swelling-induced integrin activation,14, 15 whereas the control hexapeptide GRADSP was ineffective (Fig. 1A). In line with previous data,12 TUDC induced within 1 minute phosphorylation of extracellular signal regulated kinases Erk-1/-2, which was abolished in the presence of the RGD-motif containing hexapeptide but not in presence of the inactive control hexapeptide (Fig. 2). TUDC also induced activation of the epidermal growth factor receptor (EGFR) in an RGD-hexapeptide-sensitive way (Fig. 2). TUDC-induced EGFR tyrosine phosphorylation involved tyrosine residues 845 and 1173, but not Tyr1045 (Fig. 2). Tyr845 is a known Src kinase target, which triggers an activating autophosphorylation at Tyr1173.28, 29 A similar EGFR phosphorylation pattern is induced by hypoosmotic hepatocyte swelling,30 a condition in which α5β1-integrins act as osmosensors. Swelling-induced β1-integrin activation largely occurred in the plasma membrane12 (Fig. 1B), in line with the concept that β1 integrins in the plasma membrane serve as osmo-/mechanosensors through a swelling-induced attachment to extracellular matrix proteins.

Societies and clinicians need to understand economic concepts and

Societies and clinicians need to understand economic concepts and be able to contribute positively to economic buy R428 evaluations [44]. We should not allow health economists to be the sole influence on Governments on the availability of new therapy or the maintenance or introduction of treatment regimens such as prophylaxis. It is our responsibility

as a patient community to make a contribution to these vital decisions. To do this effectively, we must be able to demonstrate the efficacy of treatment or treatment regimens using outcome data. Across the developed world there is significant variation in national funding arrangements for the treatment of haemophilia and the resulting outcomes [36]. Haemophilia care in Australia is at the upper end of funding levels and effectiveness for patients. Funding of haemophilia care in Australia is supported by a unique collaborative partnership between governments, healthcare providers and people with haemophilia to deliver a highly effective model of care. Although governments provide the majority of direct and indirect health funding to support people with haemophilia, this is within a framework of shared responsibility Y-27632 supplier that recognizes the high per capita cost of this area of healthcare. In product costs alone, Australian

governments provided funding in 2013/2014 in the order of $A170 million, representing approximately 18% of the total budget for all blood Cyclic nucleotide phosphodiesterase and blood products. This significant funding contribution is balanced by the active involvement of healthcare providers and people with haemophilia to ensure every dollar spent delivers greatest effect. This presentation outlines the Australian arrangements for supporting provision of effective care for haemophilia. In identifying the elements of these arrangements, the presentation highlights the potential benefits still to be obtained in Australia from consistent collection and recording of nationally agreed outcome measures. Australian

Funding Arrangements for the treatment of people with haemophilia consist of two main elements. The supply of product and a national framework to support improvements in clinical practice are funded under legislated National Blood Arrangements. The arrangements for delivery of care are funded by the Commonwealth and jurisdictional governments under the separate general provisions of the recently introduced National Health Reform. Under the National Blood Arrangements, the Australian Government provides 63% funding and 37% is collectively provided by state and territory governments. The National Blood Authority (NBA) is the Australian Government statutory agency that that manages the funding and represents the interests of the Australian, state and territory governments in relation to the supply of blood and blood products.

Morphological data combined with molecular evidence show that the

Morphological data combined with molecular evidence show that they constitute three new species, for which the names, P. batesiana sp. nov., P. lundholmiae sp. nov., and P. fukuyoi sp. nov., are proposed. The three new species closely resemble species in the P. pseudodelicatissima complex sensu lato. Morphologically, P. batesiana differs from other species in the complex by having a smaller part of cell overlapping in

the chain, whereas P. lundholmiae differs by having fewer poroid sectors and P. fukuyoi by having a distinct type of poroid sectors. Nucleotide sequences of the LSU rDNA (D1–D3) of the three new species reveal significant nucleotide sequence divergence (0.1%–9.3%) from each other and from other species in the P. pseudodelicatissima complex s.l. The three species are phylogenetically closely related to species in the P. pseudodelicatissima buy CP-673451 complex, with P. batesiana appearing as a sister taxon to P. circumpora, P. caciantha, and P. subpacifica; whereas P. lundholmiae and P. fukuyoi are more

Galunisertib mw closely related to P. pseudodelicatissima and P. cuspidata. The three species show 2–3 compensatory base changes (CBCs) in their ITS2 transcripts when compared to the closely related species. The ITS2 with its structural information has proven its robustness in constructing a better resolved phylogenetic framework for Pseudo-nitzschia. “
“Macroalgae of the order Laminariales (kelp) are important components of cold-temperate coastal ecosystems. Major factors influencing their distribution are light including UV radiation and temperature. Therefore, future global environmental changes potentially Tryptophan synthase will impact their zonation, distribution patterns, and primary

productivity. Many physiological studies were performed on UV radiation and temperature stress in kelp but combinatory effects have not been analyzed and so far no study is available on the molecular processes involved in acclimation to these stresses. Therefore, sporophytes of Saccharina latissima were exposed for two weeks to 12 combinations of photosynthetically active radiation, UV radiation and temperature. Subsequently, microarray hybridizations were performed to determine changes in gene expression patterns. Several effects on the transcriptome were observed after exposure experiments. Strongest effect of temperature on gene expression was observed at 2°C. Furthermore, UV radiation had stronger effects on gene expression than high PAR, and caused stronger induction genes correlated to categories such as photosynthetic components and vitamin B6 biosynthesis. Higher temperatures ameliorated the negative effects of UV radiation in S. latissima. Regulation of ROS scavenging seems to work in a compartment specific way. Gene expression profiles of ROS scavengers indicate a high amount of oxidative stress in response to the 2°C condition as well as to excessive light at 12°C.

Another potential source of uncertainty was that elevations of AL

Another potential source of uncertainty was that elevations of ALT are intermittent or unreproducible in a majority of outwardly healthy subjects,11 whereas the present results are based on single measurements of serum transaminase activities in subjects selected for iron phenotypes and HFE genotypes. The C282Y homozygotes identified by screening in this study had relatively modest serum ferritin elevations, for the most part, and are not representative of patients diagnosed

in practice. Homozygotes with heavier iron burdens and consequent hepatocellular damage may have elevated transaminases. The present results demonstrate that participants who had C282Y homozygosity uncomplicated by a liver disorder associated with inflammation (e.g., steatosis or HCV) are more likely to have normal serum transaminases and elevated serum ferritin levels. Persons with both elevated Opaganib purchase serum transaminase and elevated serum ferritin levels are less likely to be C282Y homozygotes. Thus, it is also predicted that the proportion of patients who present with both elevated serum transaminases and hyperferritinemia who are C282Y homozygotes with iron overload without

concomitant inflammatory liver disease is relatively small.8, 9, 11 Our observations and prediction are consistent with the low rates of detection of HFE C282Y homozygotes observed in liver clinics,14 because many of these homozygotes also have normal serum transaminases. In a retrospective analysis of physicians’ evaluations of 100 consecutive patients in whom mild elevations of ALT and AST were observed, evaluation to exclude hemochromatosis was not performed in 90% of subjects.15 Taken together, these Selumetinib cell line observations suggest that some physicians are reluctant

to evaluate patients for HFE hemochromatosis because they erroneously believe that this condition is typically associated with elevated serum transaminases. We conclude that all Caucasian patients with hyperferritinemia should be evaluated for HFE hemochromatosis, regardless of serum transaminases. Other tools that can aid in the detection of HFE hemochromatosis include elevated serum transferrin saturation16 and family history.17, 18 “
“Background and Aim:  HFE mutations, a common cause of hereditary hemochromatosis (HH), are reportedly associated with hepatic iron overload, severe liver fibrosis, and good response to interferon Branched chain aminotransferase treatment in European patients with chronic hepatitis C (CHC). HH shows ethnicity-based differences and little is known about the effects of HH mutations on CHC in the Japanese. Thus, the aim of this study was to clarify the clinical influence of HFE mutations in Japanese CHC patients. Methods:  In a total of 251 patients with CHC, we analyzed the frequencies of H63D and S65C mutations in the HFE gene, and the influence of these mutations on clinical parameters and response to pegylated-interferon-alpha 2b (PEG-IFN) plus ribavirin therapy. Results:  Fourteen patients (5.

Hopefully, the initiation

Hopefully, the initiation Protein Tyrosine Kinase inhibitor of the World Health Organization International Clinical Trials Registry Platform will facilitate such

assessments for future trials.41, 42 Another limitation in this review was insufficient reporting. Investigators of future trials are therefore well advised to adhere to the Consolidated Standards for Reporting of Trials in order to improve the quality of trial reports.43 These potential limitations and concerns may lower our confidence in the estimates of intervention effect. However, in our meta-analysis for SVR there is no apparent heterogeneity (I2 = 0%), and the direction of the treatment effect is the same across all included trials. Further research is unlikely to change our confidence in the estimate of the effect. It is a common misconception that large RCTs are generally more reliable than meta-analyses. The reason this misconception has prevailed is due to a number of highly

cited papers that compared high-quality large trials with collections of low-quality small trials (an unfair comparison). In empirical studies where high-quality large trials are compared with a collection of high-quality small trials, the results from the two are typically nondiscrepant. In the case of the IDEAL trial,3 the results still show an effect—albeit small—in favor of peginterferon alpha-2a. There are many examples of large trials that underestimate the treatment effect simply by chance. Current evidence suggests that peginterferon alpha-2a is significantly superior to FDA-approved Drug Library in vitro peginterferon alfa-2b regarding benefits (SVR, which is clearance of the virus from the blood). However, there is insufficient evidence to detect any differences regarding harms (mortality and adverse events). Future trials must further the correlation between achieving SVR and clinically relevant outcomes such as risk of cirrhosis, hepatocellular carcinoma, and mortality. Molecular motor We thank the patients and investigators who participated

in the included trials, with special thanks to the investigators who responded to our inquiries. We also thank our colleagues Dimitrinka Nikolova and Sarah Louise Klingenberg. “
“Dorrell C, Erker L, Schug J, Kopp JL, Canaday PS, Fox AJ, et al. Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice. Genes Dev 2011;25:1193-1203. (Reprinted with permission.) The molecular identification of adult hepatic stem/progenitor cells has been hampered by the lack of truly specific markers. To isolate putative adult liver progenitor cells, we used cell surface-marking antibodies, including MIC1-1C3, to isolate subpopulations of liver cells from normal adult mice or those undergoing an oval cell response and tested their capacity to form bilineage colonies in vitro.

Disclosures: The following people have nothing to disclose: Ammar

Disclosures: The following people have nothing to disclose: Ammar Majeed, Annika Bergquist, Gunnar Söderdahl, Maria Castedal, Karouk Said Background: Next generation sequencing Roxadustat supplier (NGS) allows the high-throughput sequencing of multiple genes in several subjects, concomitantly. This new technology should lower the cost and time of molecular analyses in hereditary cholestasis and cholelithiasis, which comprise autosomal dominant and recessive disorders, and the disease-causing genes of which contain numerous exons. NGS might also help to

identify new genes in these disorders. Aims of the study : 1) Determine the feasibility and input of a NGS strategy for the screening of the genes implicated in the recessive disorders progressive familial intrahepatic cholestasis (i.e. ABCB4, ABCB11 and ATP8B1) and Dubin Johnson’s syndrome (i.e. ABCC2); 2) Screen 5 candidate genes encoding transporters (ABCG5, HM781-36B research buy ABCG8, SLC4A2) or bile acid receptors (NR1H4, GPBAR1). Materials

and Methods: Fifty-five consecutive unrelated patients (2/3 females), referred to our national reference laboratory for intra-hepatic cholestasis or cholelithiasis genotyping, were investigated. Genomic DNA was extracted from peripheral blood. A DNA capture strategy was developed, allowing the concomitant screening of 24 patients. Each DNA was converted to a sequencing library by fragmentation, end repair, and ligation

to oligonucleotide adapters. Specific gene probes for the 154 coding exons of the 10 genes of interest were designed with the Nimblegen software. Individual library fragments were double captured and clonally amplified by solid surface bridge amplification (MiSeq sequencer). The dropGenTM VAV2 application was used to analyze the raw data of sequencing. Results: NGS was extremely time-efficient and accurate. Each analysis of 24 patients was completed within a week. Sanger sequencing confirmed all identified variants. The mean coverage was ≥96.5% with a depth of 400X. In 37 patients, variants were detected in ABCB4 (n=14), ABCB11 (n=9), ABCC2 (n=14) and/or ATP8B1 (n=5) genes. In 5 patients, 2 of these genes were mutated (e.g. ATP8B1/ABCB4). In 10 patients, the variant(s) of one of these genes were associated with variant (s) in one of the candidate genes, namely GPBAR1 (n=4), ABCG5 (n=5) or ABCG8 (n=1). The homozygous ABCB11 p.Val444Ala genotype, known to be associated with hormonal cholestasis, was detected in 20 patients. Conclusions: NGS provides multiple advantages over the classical methods for genotyping subjects with hereditary cholestasis or cholelithiasis.