001), whereas differences between early (Child A) and decompensated (Child C) cirrhosis did not reach statistical significance (Fig. 1A). The underlying disease etiology did not influence ATM inhibitor the serum fractalkine level (Fig. 1B). Moreover, the serum fractalkine level correlated with clinical scores of disease progression [r = 0.236 and P = 0.021 for Child-Pugh points and r = 0.336 and P = 0.001 for Model for End-Stage Liver Disease (MELD) scores; Fig. 1C], correlated inversely with liver function (e.g., r = −0.296 and P < 0.001 for albumin, r = 0.365 and P < 0.001 for bilirubin, r = −0.364 and P < 0.001 for cholinesterase, and r = 0.236 and P = 0.002 for the international normalized ratio), and correlated

with noninvasive quantitative selleck products fibrosis markers (r = 0.388 and P < 0.001 for hyaluronic acid and r = 0.465 and P < 0.001 for

procollagen III peptide; Fig. 1C). We next assessed the intrahepatic gene expression of CX3CL1 and CX3CR1 in patients with different stages of fibrosis by real-time qPCR. The intrahepatic expression of cx3cl1 was down-regulated when we compared nonfibrotic or fibrotic livers with cirrhotic livers (Fig. 1D). Intrahepatic cx3cr1 expression was strongly reduced in cirrhotic livers versus fibrotic or nonfibrotic livers (Fig. 1D). This finding was in sharp contrast to the increased numbers of macrophages that were observed in cirrhotic livers,17 and this suggested that the down-regulation of CX3CR1 in the cirrhotic liver (not a lack of CX3CR1-expressing

cells) was responsible for this finding. Collectively, these data demonstrate that progressive liver fibrosis in humans is associated with an increase in circulating fractalkine and a reduction of intrahepatic CX3CR1 expression. In order to address the functional role of CX3CR1 in hepatic injury and fibrogenesis, WT and CX3CR1-deficient mice were subjected to CCl4-induced liver injury. After a single injection of CCl4 and selleck compound during chronic liver injury induced by twice weekly CCl4 injections for 6 weeks, fractalkine gene expression was significantly up-regulated in the livers of WT and CX3CR1−/− mice (Supporting Fig. 1 and data not shown). At 24 and 48 hours after a single intraperitoneal administration of CCl4, WT and CX3CR1-deficient mice displayed massive hepatocyte necrosis and high ALT levels (Fig. 2A,B). However, CX3CR1−/− mice showed prolonged histological signs of injury and significantly elevated ALT levels at 72 and 120 hours (Fig. 2A,B), whereas WT animals fully recovered within 5 days after CCl4, as anticipated from previous studies.5 We next analyzed leukocyte infiltration into livers after CCl4-induced injury by FACS. In line with prolonged liver damage, CX3CR1−/− mice displayed a prolonged elevation of intrahepatic leukocytes at 72 and 120 hours, whereas intrahepatic leukocyte counts were almost normalized in WT mice at 120 hours after CCl4 treatment (Fig. 2C).

We found that, like hio embryos, WT medaka embryos that had been injected with wnt2bb-MO lacked prox1 expression (Fig. 5B). These results suggest that Wnt2bb signaling is responsible for liver specification in medaka. In conclusion, our study has shown that the hio mutation in medaka impairs liver specification by abrogating wnt2bb expression. Our data are thus the first

genetic evidence that RA signaling positively regulates liver specification by inducing wnt2bb expression. In this study, we examined the role of RA signaling during embryogenesis by characterizing medaka hio mutants. These mutants bear selleck compound an alteration to the raldh2 gene (Fig. 1) that encodes the enzyme principally responsible for RA synthesis, and we interpret that this is a nearly null mutation because the phenotypes of hio mutant are similar to that of RALDH2 morphants (Fig. 2 and

Supporting Fig. 1). LY2835219 The hio mutants exhibit two prominent phenotypes: missing pectoral fins and a small liver (Fig. 2 and Supporting Fig. 1). Work in mouse, chick, and zebrafish has shown that RA signaling from the somitic mesoderm is essential for limb induction and is mediated by the expression of downstream factors such as wnt2ba and tbx5.7–14 We show that the hio mutation in medaka leads to defects in pectoral fin development and tbx5 and wnt2ba expression (Supporting Fig. 2). Thus, our results indicate that RA signaling is crucial for fin specification in medaka and show that limb induction Methane monooxygenase signaling is conserved across a broad range of species (Fig. 6, right part). Significantly, our work has also uncovered a role for RA signaling in liver development. We have demonstrated that the hio mutation retards the formation of hepatic buds from the foregut (Fig. 3A) and causes a profound defect in liver specification (Fig. 3B). In addition, we

have shown that the wnt2bb expression required for the regulation of liver specification is undetectable in the LPM of hio embryos (Fig. 5A). Our data constitute the first genetic evidence that RA signaling regulates vertebrate liver specification by inducing wnt2bb gene expression (Fig. 6, left part). Previously, Wang et al.23 reported that liver growth is severely affected in RALDH2-deficient mouse embryos. Thus, RA signaling in liver specification may be conserved among other species. There are several similarities in the signaling pathways governing pectoral fin and liver organogenesis. During zebrafish pectoral fin development, RA signaling induces wnt2ba expression, which in turn induces tbx5 expression. Tbx5 is a key molecule that regulates the expression of downstream effectors such as the fgf and bmp family members fgf24, fgf10, and bmp2b.7, 16 Thus, limb induction requires a sequential RA Wnt Tbx Fgf + Bmp signaling cascade. A parallel situation may exist for liver specification in medaka.

This discovery complements growing evidence that Hh signaling guides repair of chronically injured livers, and it suggests that common mechanisms mediate fetal liver development and repair of adult liver injury. Therefore, progress in delineating how Hh-responsive mechanisms regulate liver growth and C59 wnt mw development might help to unravel conserved mechanisms that control regeneration

of injured livers in adults. Such knowledge has important implications for patients with various types of acute and chronic liver damage. The authors thank Dr. Xiaoling Wang (Gastroenterology, Duke University) and Dr. Gregory Michelotti (Anesthesiology, Duke University) for technical assistance, and Dr. Jiawen Huang (Gastroenterology, Duke University) for animal care assistance. The authors thank W. C. Stone (Gastroenterology, Duke University) for his administrative support

to this work. Additional Supporting Information may be selleck compound found in the online version of this article. “
“The aim of this study was to determine the safety and potential efficacy of B-cell depletion with the anti-CD20 monoclonal antibody rituximab in patients with primary biliary cirrhosis (PBC) and an incomplete response to ursodeoxycholic acid (UDCA). This open-label study enrolled six patients with PBC and incomplete responses to UDCA to be treated with 2 doses of 1000 mg rituximab separated by 2 weeks and followed for 52 weeks. The primary endpoints were safety and changes in B-cell function. Anidulafungin (LY303366) Two patients received only 1 dose of rituximab, one due to activation of latent varicella and the other due to a viral upper respiratory infection. Serum levels of total IgG, IgM, and IgA as well as anti-mitochondrial

autoantibodies (AMAs) IgA and IgM decreased significantly from baseline by 16 weeks and returned to baseline levels by 36 weeks. Stimulation of B cells with CpG produced significantly less IgM at 52 weeks after treatment compared with B cells at baseline. In addition, transient decreases in memory B-cell and T-cell frequencies and an increase in CD25high CD4+ T cells were observed after treatment. These changes were associated with significant increases in mRNA levels of FoxP3 and transforming growth factor-β (TGF-β) and a decrease in tumor necrosis factor-α (TNF-α) in CD4+ T cells. Notably, serum alkaline phosphatase levels were significantly reduced up to 36 weeks following rituximab treatment. Conclusion: These data suggest that depletion of B cells influences the induction, maintenance, and activation of both B and T cells and provides a potential mechanism for treatment of patients with PBC with an incomplete response to UDCA. (HEPATOLOGY 2012) Primary biliary cirrhosis (PBC) is a female-predominant, organ-specific autoimmune disease characterized by nonsuppurative destructive cholangitis of the intrahepatic bile ducts.

SREBP-1c coordinately regulates transcription of key enzymes involved

in lipogenesis.31 Moreover, insulin resistance in rodents and in human subjects changes the disposition of ingested carbohydrate away from skeletal muscle glycogen synthesis towards hepatic de novo lipogenesis.32 Thus, the beneficial effects of hypocaloric diets on IHL fat could be mediated in part through improved peripheral insulin resistance. Yet, whereas insulin-resistant subjects tended Epacadostat to lose more IHL compared with insulin-sensitive subjects, we did not observe a relevant interaction between insulin sensitivity and the response to macronutrient composition of the diet. We obtained similar results when we stratified our subjects for glucose tolerance. A recent clinical study in obese insulin-resistance subjects reported similar reductions in body weight and IHL after 11 weeks on a hypocaloric diet with either high or low carbohydrate content. However, the low carbohydrate diet was superior in improving hepatic insulin sensitivity.15 In our subjects an OGTT-derived index of hepatic insulin

resistance, which has to be interpreted with caution, showed no significant interaction between macronutrient composition and improvements in hepatic insulin sensitivity during the 6-month intervention. Approximately half of our subjects had an IHL content >5.6%, a value reported as “the upper limit of normal” for IHL find protocol with an increased risk of hepatic steatosis.33 Subjects exceeding this cutoff showed an ≈7-fold greater absolute reduction in IHL compared with subjects with Glycogen branching enzyme normal IHL content. Remarkably, subjects with normal and with elevated IHL content showed similar improvements in glucose metabolism,

even though the absolute reduction in IHL was much greater in the latter group. The observation may suggest that the improvement in glucose metabolism with dietary weight loss is not directly related to the quantity of mobilized IHL. The dynamics of fat mobilization may be more important in this regard. Possibly other mechanisms, such as reductions in abdominal visceral or subcutaneous adipose tissue, mediated the beneficial effect of dietary weight loss on glucose metabolism.34 Indeed, subjects with normal and with elevated IHL showed similar reductions in abdominal visceral adipose tissue. We observed larger reductions in total- and LDL-cholesterol in the reduced fat compared with the reduced carbohydrate group. Yet triglycerides, HDL-cholesterol, and measures of insulin resistance responded similarly or improved more with reduced carbohydrate diets.20 Similar to another dietary intervention study,29 circulating total and high molecular weight adiponectin tended to increase more with reduced carbohydrate diet. These findings fuel the concern that macronutrient composition of hypocaloric diets could adversely affect cardiovascular and metabolic risk.

An increase in b-ALP, osteocalcin and NTx serum levels were detected in 19 (73%), two (8%) and 10 https://www.selleckchem.com/products/LY294002.html (38%) pts respectively. The values of all other serum parameters studied were in normal range, except the reduction of creatinine clearance (53 mL/min) in one patient. With regard to urinary evaluations, an increase of piridinoline, calcium and phosphorus was

present in eight (26%), one (4%) and three (12%) pts respectively. In one pt (4%) reduced calcium levels were found. The mean BMI was 25.05 (range, 20.76–29.71). The mean WFH score was 42.5 (range, 8–71). The mean Petterson score was 24.8 (range, 4–41). The median F Z-score was –1.74 (range, −0.1/−2.8) and the median L Z-score was −1.26 (range, + 0.9/−3.0). Osteoporosis was diagnosed in four of 26 pts (15%) at F and in two of 26 (8%) pts at L sites. Osteopenia was present in 19 of 26 pts (73%) at F and in 13 of 26 pts (50%) at L sites (Tables 1 and 2). Serological and urinary markers: 19 of 26 pts (73%) showed a decrease of 25-OH Vit D serum level. An increase in PTH, b-ALP and NTx serum levels EMD 1214063 was detected in one (4%),

20 (76%) and nine (34%) pts respectively. The values of all other serum parameters studied were in normal range. With regard to urinary evaluations, an increase of piridinoline, calcium and phosphorus was present in seven (26%), three (12%) and three (12%) pts respectively. The mean BMI was 24.98 (range, 17.28–34.72). The mean WFH score was 28.2 (range, 12–63). The mean Pettersson score was 14.3 (range, 7–36). The median F Z-score was –1. 42 (range −0.1/−2.7) and the median L Z-score was −1.33 (+0.10/−2.6). Osteoporosis was diagnosed

in six of 26 pts (23%) at F and in three of 26 (12%) pts at L sites. Osteopenia Reverse transcriptase was present in 13 of 26 pts (50%) at F and in 12 of 26 pts (46%) at L sites (Tables 1 and 2). Serological and urinary markers: 23 of 26 pts (88%) showed low 25-OH Vit D serum levels. three of 26 pts (11%) had increased PTH serum levels. An increase of b-ALP, osteocalcin and NTx serum levels was detected in six (23%), one (4%) and three (11%) pts respectively. The values of all other serum parameters studied were in normal range. With regard to urinary evaluations, an increase of piridinoline, calcium and phosphorus was present in two (8%), three (12%) and six (23%) pts respectively. All complete serum and urinary results are shown in Table 3. The following parameters in the three different study groups were selected for statistical comparison: 25-OH Vit D, b-ALP and NTx, F DXA, L DXA, WFH score, Pettersson score and regimen (i.e. prophylaxis or on demand) of substitution therapy. The levels of 25-OH Vit D were homogeneously lower than normal value, without any statistically significant difference between the three groups. The WFH score was higher in co-infected (P < 0.002) and mono-infected (P < 0.

It has been determined that habit- and AZD1208 in vivo anatomy-based keys of standard taxonomic literature are largely adequate for assigning species names based on classical concepts, but they often obscure a number of cryptic and pseudocryptic species that do not conform to extra-Australian populations of the same designation, as indicated by the corresponding molecular data. Here, we present six

species (Ulva australis Aresch., U. compressa Forssk., U. fasciata Delile, U. intestinalis L., U. laetevirens Aresch., U. tanneri H. S. Hayden et J. R. Waaland) for which anatomical and molecular data were congruent with both classical concepts and GenBank accession data and confirm these as cosmopolitan taxa in Australia. We also present six putative species designations based on anatomy [U. clathrata (Roth) C. Agardh, U. flexuosa Wulfen, U. linza L., U. prolifera O. F. Müll., U. stenophylla Setch. et N. L. Gardner, U. brisbanensis sp. nov.] that are inconsistent with molecular data, suggesting novel or cryptic taxa not represented in GenBank. “
“Ninety-two strains of Microcoleus BKM120 vaginatus

(=nomenclatural-type species of the genus Microcoleus Desmazières ex Gomont) and Phormidium autumnale Trevisan ex Gomont from a wide diversity of regions and biotopes were examined using a combination of morphological and molecular methods. Phylogenies based on the 16S rDNA and 16S-23S ITS (partial) demonstrated that the 92 strains, together with a number of strains in GenBank, were members of a highly supported monophyletic clade of strains (Bayesian posterior probability = 1.0) distant from the species-cluster containing the generitype of Phormidium. Similarity of the 16S rRNA gene exceeded 95.5% among all members of the Microcoleus

clade, but was less than 95% between any Microcoleus strains and species outside of the clade (e.g., Phormidium sensu stricto). These findings, which are in agreement with earlier studies on these Adenosine triphosphate taxa, necessitate the revision of Microcoleus to include P. autumnale. Furthermore, the cluster of Phormidium species in the P. autumnale group (known as Group VII) must be moved into Microcoleus as well, and these nomenclatural transfers are included in this study. The main diacritical characters defining Microcoleus are related to the cytomorphology of trichomes, including: narrowed trichome ends, calyptra, cells shorter than wide up to more or less isodiametric, and facultative presence of sheaths. The majority of species are 4–10 μm in diameter. The possession of multiple trichomes in a common sheath is present facultatively in many but not all species. “
“Species in genus Nannochloropsis are promising candidates for both biofuel and biomass production due to their ability to accumulate rich fatty acids and grow fast; however, their sexual reproduction has not been studied.

“
“Hepatitis C Virus (HCV) entry involves at least four cellular factors, including CD81, the scavenger receptor class B type I (SCARB-1), occludin (OCLN), and claudin-1 (CLDN1). In addition, CLDN6 and CLDN9 have been shown to substitute for CLDN1 as HCV entry factors in human nonliver cells. We examined the role

of different CLDN proteins during HCV entry by using cell lines expressing either predominantly CLDN1 (Huh-7.5) or CLDN6 (HuH6). Huh-7.5 cells were susceptible to all tested HCV isolates, whereas HuH6 cells were only permissive to some viral strains. Silencing of CLDN6 in HuH6 cells revealed that these cells are infected in a CLDN6-dependent fashion, and ectopic expression of CLDN1 or CLDN6 in 293T cells lacking endogenous CLDN Idasanutlin supplier expression confirmed that only some this website HCV strains efficiently use CLDN6 for infection. CLDN1-specific neutralizing antibodies (Abs) fully abrogated infection of Huh-7.5 cells by isolates that use CLDN1 only, whereas viruses with broad CLDN tropism were only partially inhibited by these Abs. Importantly, infection by these latter strains in the presence of anti-CLDN1

Ab was further reduced by silencing CLDN6, suggesting that viruses with broad CLDN usage escape CLDN1-specific Abs by utilization of CLDN6. Messenger RNA (mRNA) levels of HCV entry factors in liver biopsies of HCV patients infected with different genotype and with variable degree of liver fibrosis were determined. Uniformly high levels of CD81, SCARB-1, OCLN, and CLDN1 mRNA were detected. In contrast, abundance of CLDN6 mRNA was

highly variable between patients. Conclusion: These findings highlight differential CLDN usage by HCV isolates, which may evolve based on variable expression of CLDN proteins in human liver cells. Broad CLDN tropism may facilitate viral escape from CLDN1-specific therapeutic strategies. (Hepatology 2014;58:24–34) Hepatitis C virus (HCV) is a highly variable, plus-strand RNA virus of the family Flaviviridae and a leading cause of liver disease, including fibrosis, cirrhosis, and hepatocellular carcinoma.[1] Farnesyltransferase The pronounced variability of HCV facilitates viral immune evasion and is attributable to enormous replication rate and error-prone RNA replication. Seven genotypes (GTs) and multiple subtypes are known, with genetic diversity being in the order of more than 30% between individual viral GTs.[2] Although the basic genome structure is conserved among HCV GTs, there are remarkable genotype-dependent differences with regard to treatment response and pathophysiology of the infection. For instance, GTs 1 and 4 exhibit inferior response rates, when compared with GTs 2 and 3, in interferon-based therapy regimens, and GT3 virus infection shows a particularly strong association with liver steatosis.

Multifocal and diffuse lesions express GLUT-1, which may biologically Ipatasertib distinguish

them from focal lesions.[200] With diffuse lesions, the liver is almost completely occupied by hemangiomas and symptoms include respiratory insufficiency due to an abdominal mass effect, abdominal compartment syndrome, coagulopathy (Kasabach-Merritt syndrome), multiorgan system failure, and hypothyroidism due to overproduction of type 3 iodothyronine deiodinase which converts thyroid hormone to its inactive form.[201] Diffuse hemangiomas often do not respond to steroid therapy[202] and most require surgical resection or beta-blocker therapy to improve hematologic parameters. Hepatic artery ligation and embolization have limited effect. Other treatment options for diffuse lesions include vincristine,[203] actinomycin, and cyclophosphamide and propranolol.[204] 48. Liver transplant evaluation for IH is indicated if the hemangioendothelioma is not responding to treatment or is associated with life-threatening complications. (1-B) 49. Candidates being considered for LT for a hemangioendothelioma should be screened

for hypothyroidism. (2-B) Liver disease is present in up to 35% of cystic fibrosis (CF) patients, but only 5-10% of patients have selleck compound cirrhosis.[205, 206] Ursodeoxycholic acid therapy is recommended, although its impact on the progression of CFLD is not known.[207-209] Endstage liver disease is characterized by coagulopathy and hypoalbuminemia and is not attributable Ribose-5-phosphate isomerase to malabsorption. Portal hypertensive-related hemorrhage alone, in the absence of other signs of decompensated liver disease, may not be a sufficient indication for LT in CF patients, as alternative therapies may be equally acceptable.[210-212] Optimal timing for isolated LT involves careful assessment of cardiopulmonary function, infections,

and nutritional status in CF patients. Currently, Model for Endstage Liver Disease (MELD) / Pediatric Endstage Liver Disease (PELD) exception points are permitted for those patients with CF whose pulmonary function tests (PFTs) are <40% of predicted FEV1.[213, 214] Five-year posttransplant survival rates for CFLD are lower than for those who underwent transplantation for other etiologies. Compared to those patients remaining on the waiting list, pediatric and adult transplant recipients with CF gained a significant survival benefit.[215] A different analysis of the UNOS database and various single center reports convey similar patient and graft survival data among patients with CF.[212, 216, 217] While LT may improve pulmonary function and nutritional status,[218, 219] CF patients may be at higher relative risk for the development of posttransplant diabetes mellitus and renal impairment.[220-223] 50. The indications for liver transplantation in CF are guided by the degree of hepatic synthetic failure and the presence of otherwise unmanageable complications of portal hypertension.

A study looking at the effect of dietary fish oils on Helicobacter-induced colitis and colitis-associated

colon cancer was also undertaken using the Smad3 model [51]. Contrary to expectation, mice consuming diet containing the dietary fish oils showed higher levels of inflammation and dysplasia, indicating that they were less equipped to mount a successful response against H. hepaticus. The potential use of polysulfated polysaccharides to prevent enterohepatic C646 Helicobacters adherence to host cells was also investigated [52]. The importance of sulfated heparin was clearly demonstrated to inhibit adherence of the Helicobacter species, with fucoidan seen to be the most effective at impairing adherence by all Helicobacter tested. Two molecular genus-specific methods were developed to detect Helicobacter spp. in human colonic tissue. Examining FISH and PCR analyses

on 109 colonic biopsy samples revealed a correlation rate of 68%. In a large proportion of cases, the discordant results were on account of FISH yielding positive results as opposed to PCR, suggesting that it may be a more sensitive test [30]. A Western blot analysis to detect antibodies against H. hepaticus in sera was also described [25]. A triplex PCR was developed allowing the detection MI-503 order of Pseudomonas aeruginosa, H. hepaticus, and Salmonella Typhimurium in mice. All three bacteria were successfully detected in liver, feces, and cecum of experimentally infected mice [53]. A commercially available colorimetric fecal dipstick assay for the detection of H. hepaticus was also evaluated in mice but was shown to lack sensitivity Glycogen branching enzyme [54]. McIntosh et al. [55] modified the urea concentration and pH indicator of a urease test to improve the in situ detection and localization

of non-H. pylori Helicobacters, however without exact species identification. An 8-week treatment of a commercial 4-drug diet containing amoxicillin, clarithromycin, metronidazole, and omeprazole showed promising results in eradicating Helicobacter spp. from immunocompromised mice [56]. In conclusion, significant advances have been made over the last year in “other than H. pylori” Helicobacter research especially in the elucidation of their immunogenic potential. This provides huge potential to continue to elucidate the role of these organisms in health and disease. The authors have declared no conflicts of interest. “
“Background:  We examine the effect of eradicating Helicobacter in idiopathic parkinsonism (IP). Marked deterioration, where eradication-therapy failed, prompted an interim report in the first 20 probands to reach de-blinding. The null-hypothesis, “eradication has no effect on principal outcome, mean stride length at free-walking speed,” was rejected. We report on study completion in all 30 who had commenced post-treatment assessments.

7 The main radioactive agent integrated with microspheres for radioembolization or selective internal radiotherapy (SIRT) is yttrium-90 (Y-90), although other agents have been reported. To date, two products for radioembolization with Y-90 microspheres are commercially available, based on resin or glass. Due to a smaller size and a significantly higher amount of radioactivity per single sphere,8 glass microspheres do not show embolizing effects on larger tumor vessels. This limits exposure to surrounding liver tissue and allows glass microspheres to be utilized

in the presence of portal vein thrombosis.7 We report the analysis of 108 consecutive cases with intrahepatic advanced HCC treated with Y-90 glass microsphere radioembolization. The selleck chemical aim of this study was to provide evidence on the safety of this therapy www.selleckchem.com/products/jq1.html in this particular group of patients and to determine long-term survival, which has to be considered the most significant clinical endpoint. AE, adverse event; AFP, alphafetoprotein; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma; MAA, macroaggregated albumin;

PVT, portal vein thrombosis; RECIST, Response Evaluation Criteria in Solid Tumors; SIRT, selective internal radiotherapy; SPECT, single photon emission computed tomography; TACE, transarterial chemoembolization; BCKDHA Tc-99, technetium-99; TTP, time to progression; RILD, radiation-induced liver disease; Y-90, yttrium-90. In all, 108 consecutive patients with advanced HCC who were treated with radioembolization with Y-90 glass microspheres at a single center (University Hospital Essen, Germany) between November 2006 and March 2009 were included in this observational

cohort study. The indication for Y-90 treatment was driven by an institutional algorithm based on the BCLC treatment scheme. Patients were routinely staged by a 3-phase computed tomography (CT) or magnetic resonance imaging (MRI) of the liver, a contrast-enhanced ultrasound to further determine vascularity, as well as a CT of the lungs. If alphafetoprotein (AFP) was >400 ng/mL, patients additionally received a technetium-99 (Tc-99)-based bone scan. The major clinical features allowing Y-90 treatment and therefore inclusion into this observational study were nonresectability of HCC and BCLC C tumor stage. Patients with BCLC A and B were also included if they were not eligible for selective TACE. Additional inclusion criteria were adequate hypervascularity (concentration and consecutive “blush” of contrast agent in the arterial phase of CT and/or contrast-enhanced ultrasound), a liver function with a Child-Turcotte-Pugh (CTP) score ≤7 points, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.