This is also the first report to show that direct addition of RCA blockers into plasma samples from patients chronically infected with HCV render endogenous plasma virions sensitive to complement-mediated destruction. This strategy may be further Palbociclib datasheet developed in combination with the current standard of care for treatment of chronic HCV (pegylated

IFN-α plus ribavirin) to enhance therapy efficacy. We thank Apath (Brooklyn, NY) and Dr. Charles M. Rice at Rockefeller University (New York, NY) for JFH-1, pFL-J6/JFH, and Huh7.5.1 cells. Additional Supporting Information may be found in the online version of this article. “
“Background and Aim:  Confocal laser endomicroscopy (CLE) is a new endoscopy technique for subsurface analysis of the gastric mucosa and in vivo histology examination during endoscopy. We aimed to compare the clinical applicability and predictive power of CLE with the diagnosis of Helicobacter pylori infection in patients with gastrointestinal symptoms. Methods:  A total of 103 consecutive patients scheduled to undergo endoscopy were enrolled. CLE image criteria for H. pylori infection were established in a pilot study of 20 patients, then images for 83 consecutive patients were prospectively evaluated, and data were correlated with the final diagnosis of H. pylori infection in a blinded manner. Results: 

We found good association between histopathology and CLE findings. H. pylori infection was identified by CLE with

any of the NVP-AUY922 solubility dmso following three features: white spots, neutrophils and microabscesses. The accuracy, sensitivity and specificity of CLE diagnosis of H. pylori infection were 92.8%, 89.2% and 95.7%, respectively. The mean κ-value for interobserver agreement in the prediction of H. pylori infection was 0.78. Neutrophils were the best diagnostic feature and had good sensitivity (83.8%) and specificity (97.8%). H. pylori-associated changes were more common in the antrum than in the corpus among infected patients (P < 0.001). Conclusions: H. pylori infection can be identified by specific cellular and subcellular changes of the surface gastric mucosa with CLE. CLE is a novel, useful method for predicting H. pylori infection in vivo during endoscopy. Helicobacter pylori colonizes selleck chemical the gastric mucosa of over half of the world’s population, making it one of the most prevalent infections.1H. pylori infection is the major cause of gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma and gastric cancer.2 Correct diagnosis is therefore critical for treatment and to prevent potential complications. Recently, confocal laser endomicroscopy (CLE) has been developed to realize in vivo histology. CLE combines standard video endoscopy with confocal microscopy imaging of gastrointestinal mucosa during endoscopy.

7A), verifying the improvement of insulin signaling. Consistently, treatment of H4IIE cells with IsoLQ (5-20 μM) or LQ (10-100 μM) effectively prevented the serine phosphorylation http://www.selleckchem.com/products/CAL-101.html of IRS1 (Fig. 7B). The inhibition of IRS1 serine phosphorylation by IsoLQ or LQ was also confirmed in other cell models such as HepG2 cells, C2C12 myotubes, 3T3-L1 adipocytes, and primary rat hepatocytes (Fig. 7C). To further assess

the effect of IsoLQ or LQ on glucose homeostasis and insulin sensitivity, each agent was administered to mice fed an HFD: treatment of mice with the agents at the dose of 10 or 30 mg/kg/day for 5 days during the last 5 weeks of total 11 weeks of HFD feeding displayed a significantly improved glucose tolerance (2

g glucose/kg) compared to vehicle-treated control (Fig. 8A; normal diet [ND] and HFD controls were shared to simultaneously compare the compound effects), showing their effects on systemic insulin sensitivity. In mice fed an HFD for 9 weeks, IsoLQ treatment almost completely reduced fasting glucose, fasting serum insulin levels, and HOMA-IR values (Fig. 8B, upper). Similar results were obtained using Lepob/ob mice (Fig. 8B, lower). Our results indicate that licorice flavonoids have the ability to reduce obesity-induced insulin resistance. As a continuing effort to assess the effect of IsoLQ or LQ on insulin action, we measured glucose production and uptake in representative cell models. Incubation of HepG2 cells with each agent resulted in a significant decrease in glucose production, which IWR-1 research buy was comparable to that caused by insulin (Fig. 8C, left). TNF-α inhibited an increase in glucose uptake by insulin in C2C12 myotubes or differentiated 3T3-L1 adipocytes, which was also abrogated by IsoLQ treatment (Fig. 8C, middle and right). Our results indicate that IsoLQ (or LQ) treatment prevents glucose production from hepatocytes and stimulates glucose uptake into selleckchem muscle

cells or adipocytes. In HFD-fed mice, we measured the levels of glucose 6-phosphatase (G6Pase) mRNA as a marker of gluconeogenesis. IsoLQ or LQ treatment inhibited the G6Pase gene induction (Fig. 8D, upper). Consistently, either IsoLQ or LQ treatment antagonized the ability of cyclic adenosine monophosphate (cAMP) and dexamethasone to increase G6Pase mRNA levels in primary rat hepatocytes, as did insulin (Fig. 8D, lower). These results demonstrate that the inhibition of glucose production by IsoLQ or LQ may be mediated by the suppression of G6Pase. PTP1B negatively regulates insulin signaling by catalyzing the dephosphorylation of IR and IRS1/2.5 A decrease in PTP1B activity accompanies improved insulin sensitivity in obese subjects.18 In addition, evidence is accumulating that PTP1B polymorphisms in humans might be associated with insulin resistance.

Genetic links to hemochromatosis were first reported in 1976 and, in 1996, a strong association was reported with the C282Y mutation in the HFE gene. Knowledge of the relationship between the mutation and excessive iron absorption is incomplete but involves up-regulation of the

divalent metal transporter protein, low levels of a polypeptide called hepcidin and up-regulation of a basolateral transport protein called ferroportin. Organs with the highest levels of transferrin receptors are at highest risk for damage by free radicals released by non-transferrin bound iron (free iron). Despite these important developments, most patients are treated by regular venesection, usually removal of 400-500 ml of blood that contains approximately Selleck STI571 250 mg of iron. The patient illustrated selleck inhibitor below was a woman, aged 53, who was investigated because of malaise and intermittent abdominal pain. On examination, she appeared to have prominent skin pigmentation. Liver function tests were abnormal and her serum ferritin was elevated at 834 µg/l. She subsequently developed symptoms of adrenal insufficiency and was commenced on steroid replacement therapy. Genetic testing revealed a homozygous C282Y mutation

while her liver biopsy showed grade 4 iron deposition mainly around the portal tracts. This has been highlighted in Figure 1 using a Perl’s stain. She did not have cirrhosis. Venesection on 41 occasions over 2 years resulted in a fall in ferritin to 28 µg/l. Over the subsequent 2 years, venesection was performed on 6 occasions and was associated with a serum ferritin of <50 µg/l. A liver biopsy selleck chemical was repeated 5 years after diagnosis and was normal without any evidence of iron deposition

(Perl’s stain, Figure 2). In hemochromatosis, the number of venesections required to achieve iron depletion is variable but, in one large study, the mean number was 85. Initially, all patients should have venesection at least once per week and, after iron depletion, at intervals of 1-3 months. There is now clear evidence that iron depletion improves prognosis. For example, in the absence of cirrhosis, treated patients with hemochromatosis have a similar life expectancy to that in the general population. Contributed by “
“Esophageal strictures can be caused by acid, radiation, eosinophilic esophagitis (EoE), and caustic injury. Food impaction in a young man warrants evaluation for eosinophilic esophagitis. Savary dilation is the most cost-effective therapy. Stricture dilation should be cautious (rule of threes) early on, especially in caustic, radiation and EoE strictures. Complex/resistant strictures may require steroid injections, incisional therapy, and stent placement. Complications of stricture treatment are rare. “
“We read with great interest the article by Bangarulingam et al.

[16, 17] RFA is one of the most recent local ablative therapies for small HCC[13, 14, 18], which can be performed by percutaneous or surgical approach.[19-21] For small HCC nodules (less than 3 cm), there is still some controversy regarding to the long-term effectiveness between the two treatment modalities, such http://www.selleckchem.com/products/GDC-0980-RG7422.html as overall survive time, disease-free time, and the tumor recurrence rate.[13, 22] The aim of

this randomized study was to determine which treatment modality, hepatectomy, or percutaneous RFA is more beneficial for patients with small HCC in terms of long-term outcomes. One hundred twenty patients with HCC ≤ 3 cm between January 1, 2000 and December 30, 2012 were randomized into either percutaneous RFA therapy or hepatectomy group, as initial treatment Selleckchem Enzalutamide in Sir Run Run Shaw Hospital. Sixty patients who received hepatectomy were treated at Department of General Surgery, and 60 patients who received

RFA were treated in Department of Medical Oncology. The treatment and data collection were approved by Ethical Committee of our institution. HCC diagnosis was based on the criteria used by the European Association for the Study of the Liver, confirmed by a core biopsy before therapy. This study included 88 men and 32 women with a median age of 53.4 ± 10.9 years (range: 18–71). All patients were Chinese. Inclusion criteria as follows: (i) ≥ 18 years; (ii) any solitary HCC ≤ 3 cm in diameter and no more than three tumor nodules; (iii) no extrahepatic metastasis at diagnosis; (iv)

no radiologic evidence of major portal/hepatic vein branches invasion; (v) liver function equal or better than Pugh–Child Class B, with no history of encephalopathy, ascites refractory to diuretics or variceal bleeding (Patients with Pugh–Child Class C could be enrolled after the liver function was improved to B with the treatment options, including find more albumin infusion, diuretics, and non-steroidal anti-inflammatory drugs); and (vi) platelet count > 50 × 109/L without clinical significant portal hypertension and esophageal varices. We compared the randomized analysis based on the clinical characteristics, including age, sex, Child–Pugh classification, hepatic cirrhosis, tumor anatomical location, and HBV infection. Sixty patients underwent hepatectomy for HCC. Hepatectomy procedures were performed based on the position of HCC under general anesthesia, including nonanatomic hepatectomy in 38 patients, right hepatectomy in 13 patients, and left hepatectomy in 9 patients. A nonanatomic resection aiming at a resection margin of at least 2 cm was performed.

Several studies have shown that elevated plasma FGF21 levels are found in subjects with disorders related to obesity and insulin

resistance. We aimed to assess the role of FGF21 as a potential biomarker for the diagnosis of NAFLD and/or NASH. Methods: We recruited 204 patients with and 24 without NAFLD (51 ±1 vs.50±3 years [p=0.69], male: 72% vs.58% PI3K Inhibitor Library research buy [p=0.24], 34.1 ±0.3 vs.29.3±1.0 kg/m2 [p<0.01]) and measured: 1)plasma FGF21 and cytokeratin-18 fragments (CK-18) levels, 2) liver fat by magnetic resonance imaging and spectroscopy (MRS), 3) hepatic insulin resistance index (HIRi=fasting plasma insulin x endogenous glucose production) and adipose EX 527 molecular weight tissue insulin resistance index (ATIR= fasting plasma insulin x free fatty acids), 4) muscle insulin sensitivity (Rd) during a high-dose insulin euglycemic clamp, and 5) liver histology (biopsy) (n=159). Results: Plasma levels of FGF21 were significantly

increased in patients with NAFLD (337 [217-526] vs.153 [92-323] pg/ml, p<0.001). However, FGF21 only showed moderate correlations with liver fat (r=0.26, p<0.001), HIRi (r=0.26, p=0.002), ATIR (r=0.23, p<0.001) and Rd (r=-0.35, p<0.0001). As a stand-alone test for the diagnosis of NAFLD, FGF21 had rather disappointing results. With the optimal cut-off point of 205 pg/ml we obtained a sensitivity of 78% (71-84%) and specificity of 63% (41一81%). Positive and negative predictive values were 94% (89-97%) and 28% (17-42%),

respectively. Patients with NASH had higher levels of FGF21 when compared to patients with simple steatosis on liver biopsy (386 [252-581] vs.328 [170—451] pg/ml, p=0.03). However, correlations between check details FGF21 and NAFLD activity score (r=0.22, p<0.01) and fibrosis stage (r=0.30, p<0.001) were weak. As a tool for the diagnosis of NASH (optimal cut-off point: 376 pg/ml), FGF21 also showed unsatisfactory results, with low sensitivity (53% [43 62%]) and specificity (67% [50 一 81%]). With the combined use of CK-18 and FGF21 for the diagnosis of NASH, sensitivity improved slightly to 57% (49-66%) and specificity to 85% (70-94%). However, these results were similar to the ones of CK-18 alone (sensitivity 46% [38-53%] and specificity 86% [73-95%]). Conclusions: Plasma FGF21 levels were only moderately correlated with different measures of insulin resistance, hepatic steatosis and liver histology. Based on these findings, FGF21 is not a useful stand-alone test (or combined with CK-18) for the diagnosis of NAFLD or NASH.

With commercial lyophilized normal and pathological plasmas VWF: Ag and VWF:RCo assays performed on both analysers exhibited low levels of inter-assay imprecision (AcuStar: CV% range 3.3–6.9; TOP500: CV% range 2.6–6.3). Samples from normal healthy subjects (range: VWF:Ag 44.6–173.9 IU dL−1; VWF:RCo 43.1–191.5 IU dL−1) and patients (range: VWF:Ag <0.3–115.1 IU dL−1; VWF:RCo <0.5–57.2 IU dL−1) showed a good correlation between the two VWF:Ag and VWF:RCo methods (rs = 0.92 and 0.82 respectively), with only a few inconsistent

cases among the patients’ samples evaluated. The chemiluminescent assays had a lower limit of detection for both VWF:Ag and VWF:RCo compared to immunoturbidimetric tests (0.3 IU dL−1 vs. 2.2 IU dL−1 and 0.5 IU dL−1 vs. 4.4 IU dL−1 respectively). The TOP500 and AcuStar VWF:Ag and VWF:RCo assays were precise and compare well between Venetoclax concentration centres, making these systems suitable for the Dinaciclib diagnosis of VWD in non-specialized and

reference laboratories. “
“This chapter contains sections titled: Introduction Bleeding patterns and severity of hemophilia Bleeding pattern in severe hemophilia Review of other factors that may influence hemostasis Environmental factors Discussion Conclusion References “
“Summary.  Although individuals with haemophilia have benefited from advances and the availability of safe, effective factor replacement products, high treatment costs and insurance coverage limits remains a significant concern among persons

with this disease. Many uninsured haemophiliacs turn to emergency rooms for treatment and/or patient assistance programmes for treatment of a bleed or injury. However, neither of these options is a sustainable solution for managing the care this website of patients with this costly disease. This study was conducted to examine the use of factor assistance programmes and estimate annual amounts of factor dispensed by each programme along with their associated costs. Retrospective review of pharmacy and medical record of all patients who attended the Gulf States Hemophilia and Thrombophilia Center, and who were enrolled in any factor assistance programme(s) between January 2007 and December 2010 was performed. During the 4-year observation period, approximately 19% of the centre’s haemophilia patient population was enrolled and received free factor products from at least one patient assistance programme. In addition, approximately 9.1 million dollars (US) worth of factor replacement therapy was donated to our patients during the study time. Although assistance programmes have helped many uninsured individuals with haemophilia to receive free factor products, they are not an enduring answer to the insurance problems many of our patients face.

Multiple changes have been identified previously in

dolphins during feeding and fasting states. Dolphins fasted overnight have higher serum glucose, platelets, gamma-glutamyl transpeptidase, and alkaline phosphatase; shifts toward a metabolic acidotic state; and lower serum uric acid compared to those that had recently fed (Venn-Watson and Ridgway 2007). These changes mimicked those found in people with and without diabetes (Androgue et al. 1982, Maxwell et al. 1986, Chitre and Valskar 1988, Andre et al. 2006, Nan et al. 2007). Indeed, dolphins have a diabetes-like metabolism, in which ingested sugars or high-protein fish meals lead to a sustained hyperglycemia lasting 5–10 h (Ridgway et al. 1970, Venn-Watson et al. 2011). Interestingly, endogenous nitric oxide can be impaired in people with diabetes, including reduced nitric oxide Y-27632 availability (Honing et al. 1998). The differences in nitric oxide levels found in the breath of fed vs. fasted dolphins should be further Histone Acetyltransferase inhibitor evaluated to better understand the impacts of the dolphin’s high protein diet and their diabetes-like metabolism.

A primary driver of the current study was to assess the use of breath analysis as a noninvasive indicator of cetacean health, including detection of early stages of pneumonia. In addition to general evaluation of metabolism and lung function, volatiles in the breath have been employed as “fingerprints” for detecting disease in other animal models. Carbon

dioxide, oxygen, nitric oxide, carbon monoxide, hydrogen sulfide (and other sulfides), find more acetone and other volatiles may be useful in diagnosis of lung injury and numerous metabolic or infectious diseases (Phillips 1992, Kharitonov et al., 1996, Phillips et al. 2003). The successful detection of NO in exhaled dolphin breath opens the possibility of using NO as a clinically relevant diagnostic test. In this study, a dolphin with chronic disease, including gastrointestinal disease of unconfirmed origin and a Mycoplasma-associated pneumonia, had higher postprandial exhaled NO compared to postprandial breath from healthy controls. There were no differences in exhaled NO, however, when comparing another case dolphin with chronic coccidiodomycosis with healthy controls. Reasons for this difference may be the severity of infection or inflammation, organ systems involved, or pathogen. Further studies are needed to better understand under what conditions NO may successfully detect disease in dolphins and why, in this study, significant differences between the case dolphin and healthy control dolphins were not apparent until postprandial samples were compared. Digestive state and disease detection should be considered when examining dolphins for different diseases. Standardized methodologies for sample collection will continue to be needed if NO in breath is to be used for illness detection and comparability across populations and time.

IL12 is a key candidate for treating malignancies because it is a potent proinflammatory

cytokine, activates T and NK cells, and induces the expression of IFN-γ expression. Although promising in the treatment of malignancies, especially micrometastic lesions, high Gefitinib datasheet toxicity and fatalities were observed in clinical trials mainly due to IFN-γ expression. Therefore, control of excessive induction of IFN-γ may be achieved by using gene therapy instead of an acute dose of recombinant IL12 therapy. Even with gene therapy, a high dose and frequent administrations could trigger liver toxicity; however, IL12-induced toxicity can be prevented or even treated by using IL30, as we discovered in this study. This

observation may be translated to human clinics for safely using IL12 or other proinflammatory cytokine therapy. This conclusion was further supported by the fact that IL30 significantly reduces the ConA-induced liver injury, as reported in this study, and also in agreement with the fact that ConA causes less toxicity in EBI3 knockout mice than in wildtype mice.23, 24 Importantly, multiple lines of evidence from our study suggest that IL30, as an independent cytokine, inhibits IL12-induced liver injury due to the independence of IL27 and EBI3 signaling pathways. This unique discovery reveals that IL30 perhaps is an important therapeutic candidate for preventing not only IL12 and IFN-γ, but other inflammatory cytokine-induced see more liver toxicity. IFN-γ plays a crucial role not only in initiating

innate and adaptive immune responses but also in homeostatic functions that limit inflammation-associated tissue destruction. IFN-γ’s ability to initiate an adaptive immune response is well understood and occurs mainly by way of activation of macrophages and immune cells at the site of inflammation; however, how IFN-γ maintains a crucial role in homeostatic functions is not fully understood. Because IFN-γ administration at the site of the inflammation exacerbates diseases selleck screening library in arthritis and autoimmune diabetes models, yet a lack of IFN-γ seems to enhance the severity of arthritis in the K/BxN model,32 IFN-γ is a key mediator for up-regulation of antiinflammatory cytokines, which are necessary to decrease tissue destruction. So, understanding which particular molecules are signaling downstream of IFN-γ has important therapeutic implications. Our study not only confirms that IFN-γ induces IL30 in vitro but also reveals the biological function of this cytokine. Different from Liu et al.,30 who established that IFN-γ induces IL30 in macrophages in vitro, we found that IL30 is a very potent inhibitor of proinflammatory cytokine-induced hepatotoxicity in vivo.

Among the 664 miRNA species included in the array, 374 miRNAs had expression

detected in more than 50% of the specimens, including 212 miRNAs that were consistently detected in all specimens, and were therefore selected for further investigations. On the other hand, 290 miRNAs with a detection rate less than 50%, including 151 miRNAs that were not detected in any samples tested, were excluded from the study (Supporting Fig. 1A,B). The miRNA expression profiles in the paired nontumorous livers, primary HCCs, and venous metastases were analyzed by unsupervised clustering approach. As shown in Fig. 2, the nontumorous liver samples exhibited a distinct miRNA expression profile and was clearly separated from their corresponding primary HCCs and venous metastases in the clustering analysis. However, the clustering analysis was not able to segregate venous metastases from the primary HCC samples. Primary HCCs and venous metastases from the IWR1 same patients often clustered together, indicating that the miRNA Ibrutinib supplier expression profiles of primary HCCs and corresponding venous metastases were similar. To further investigate the miRNA deregulation in hepatocarcinogenesis and metastasis, the expression changes of individual miRNA (i.e., ΔΔCt) were plotted against their statistical significance (P value, paired t test) across different sample groups in volcano diagrams. To maintain the statistical stringency in multiple comparisons,

tests were considered significant when P < 1.34 × 10−4 (based on Bonferroni correction). When comparing 20 pairs of primary HCCs with their corresponding nontumorous liver samples, learn more significant deregulation was observed in 30 miRNAs, 23 of which were significantly down-regulated in primary HCC

samples, and 7 of which were up-regulated (Fig. 3A and Table 1). miR-139-5p and miR-18a were the most significantly down- and up-regulated miRNAs, respectively. These 30 miRNAs, representing the most deregulated miRNAs in primary HCC, could be used as a specific miRNA signature for primary HCC. To determine whether miRNA deregulation contributes to HCC metastatic growth, we compared the miRNA expression levels between paired primary HCCs and venous metastases by volcano plot as described above. However, we found that no miRNA reached the Bonferroni adjusted significance level, indicating that there was no significant deregulation of individual miRNAs between primary HCCs and venous metastasis. However, a global trend of miRNA down-regulation was evidently observed in venous metastases (Fig. 3B). Using a one-sample t test to interrogate the global miRNA expression changes between the nontumorous livers, primary HCC, and venous metastases, we found that venous metastases exhibited a significant global miRNA down-regulation of approximately 0.5ΔΔCt (equivalent to 30% of miRNA expression) when compared with either the nontumorous livers and primary HCCs (P < 0.0001 for each).

PA and TR were involved with the consensus concept and design, acquisition of data, drafting of the manuscript, critical revision of the manuscript,

and participation in electronic and face-to-face voting. CK, RP, JM, DS, LP, AS, PP, TA, DR, AM, SP, PK, MR, and MK were involved with drafting of the manuscript, critical revision of the manuscript, and participation in electronic and face-to-face voting. TI was involved with drafting of the manuscript, critical revision of the manuscript, and participation in electronic voting. NP, ST, SA, BD, HW, EO, DL, and PM were involved with critical revision of the manuscript, and participation MAPK inhibitor in electronic and face-to-face voting. KG and BO were involved with

critical revision of the manuscript and participation in electronic voting. SC and AJ were involved with study supervision and participation in electronic voting. VB was involved with study supervision. Surgeon—Amit Maydeo, Thawatchai Akaraviputh, Thawee Rattanachu-ek, AZD6738 ic50 Vajarabhongsa Bhudhisawasdi Gastroenterologist—Rungsun Rerknimitr, Pises Pisespongsa, Takao Itoi, Christopher J L Khor, Ryan Ponnudurai, Jong H Moon, Dong Wan Seo, Duvvuru Nageshwar Reddy, Apichat Sangchan, Pradermchai Kongkam, Nonthalee Pausawasdi, Siriboon Attasaranya, Dong Ki Lee, Bancha Ovartlarnporn, Suraphol Churnratanakul, Kean-Lee Goh, Benedict Devereaux,

Hsiu-Po Wang, Evan Ong, Sombat Treeprasertsuk, Maylene Kok Diagnostic radiologist—Linda Pantongrag-Brown Interventional radiologist—Sundeep Punamiya, Akkawat Janchai Surgeon—Amit Maydeo, Thawatchai Akaraviputh, Thawee Rattanachu-ek Gastroenterologist—Rungsun Rerknimitr, Pises Pisespongsa, Christopher J L Khor, Ryan Ponnudurai, Jong H Moon, Dong Wan Seo, Apichat Sangchan, Pradermchai Kongkam, Nonthalee Pausawasdi, Siriboon Attasaranya, Dong Ki Lee, Benedict Devereaux, Hsiu-Po Wang, Evan Ong, Sombat Treeprasertsuk, Mohan Ramchandani, Maylene Kok Diagnostic radiologist—Linda Pantongrag-Brown Interventional radiologist—Sundeep Punamiya selleck inhibitor (All face-to-face meeting participants participated in the first two electronic votes) Members of the group were selected by the following criteria: Demonstration of knowledge/expertise in HCCA by publication/research or participate in national or regional guidelines. Geographical representation of the Asia–Pacific countries/region. Diversity of clinical views on management of HCCA (limited to clinicians). Representative countries were Australia, Malaysia, India, Taiwan, the Philippines, South Korea, Japan, Singapore, and Thailand. Representatives from China, New Zealand, and Indonesia were invited but did not participate.