AUROC, area under the receiver operating characteristic; CHC, chronic hepatitis C monoinfection; IQR/M, interquartile range/median; LSE, liver stiffness evaluation; NAFLD, nonalcoholic fatty

liver disease. Two populations with liver biopsy and LSE were included in the present study. The first population was composed of patients with chronic liver disease recruited in three French centers between 2004 and 2009 (Angers: n = 383; Bordeaux: n = 309; and Grenoble: n = 142). Patients included in the Angers and Bordeaux centers had various causes of chronic liver diseases, whereas those from Grenoble had CHC. CHC patients of the three centers (n = 467) have been included in previous studies.8, Y-27632 9 The second population was that of the multicenter ANRS/HC/EP23 Fibrostar study promoted by the French National Agency for Research in AIDS and Hepatitis.3 The patients included in both populations were identified and ultimately grouped as a single observation for statistical analyses. All patients gave written informed consent. The study protocol conformed to the ethical guidelines of the current Declaration of Helsinki and received approval from the local Ruxolitinib Ethics Committees. Liver

fibrosis was evaluated according to Metavir fibrosis (FM) staging. Significant fibrosis was defined as Metavir FM≥2, severe fibrosis as Metavir FM≥3, and cirrhosis as Metavir FM4. In the first population, histological evaluations were performed in each center by blinded senior pathologists specialized in hepatology. In the Fibrostar study, histological lesions were centrally evaluated by two senior experts with a consensus reading in cases of discordance. Fibrosis staging was considered as reliable when the liver specimen length was ≥15 mm and/or portal tract number ≥8.10 Precise definitions are provided in the Glossary in the Supporting Material. LSE by Fibroscan (Echosens, Paris, France) was performed with the M probe and by an experienced observer (>50 examinations

before the study), blinded for patient data. A time interval of ≤3 months between liver biopsy and LSE was considered acceptable for the purposes of the study. Examination conditions were those recommended this website by the manufacturer,11 with the objective of obtaining at least 10 valid measurements. Results were expressed as the median and the IQR (kPa) of all valid measurements. According to the usual definition, LSE was considered reliable when it included ≥10 valid measurements with a success rate ≥60% and IQR/M ≤0.30. LSE median was interpreted according to the diagnostic cutoffs published in previous studies. As CHC was the main cause of liver disease in our study population (68%), we tested the cutoffs published by Castera et al.12: ≥7.1 kPa for FM≥2 and ≥12.

The largest trial5 alone represented nearly 70% of observations. Based on that trial, past research has shown no difference between peginterferon alfa-2a and peginterferon alfa-2b with respect to SVR. This underlines the importance of sensitivity analyses for examining the robustness of Awad et al.’s conclusions. Because the authors showed that there was no evidence of heterogeneity (I2 = 0) among the eight studies that they included, a fixed effects model

approach is appropriate. I applied a fixed effects exact inference procedure (proposed by Tian et al.6) as a sensitivity analysis to the data shown in Fig. 2 of Awad et al.’s article. This method is unbiased even for Selleckchem Tanespimycin small samples or when only a small number of studies are included in the meta-analysis. This robust method yielded a 95% confidence interval for

the risk ratio of 0.988-1.214, which included the null value of 1. A similar analysis limited to the approved starting dose of 1.5 μg/kg/week (which excluded 1016 of the 3070 patients in the IDEAL trial) also showed a lack of a statistically significant difference with an exact 95% confidence interval of 0.967-1.214. The discrepancy between the findings based on large sample methods and those based on exact methods emphasizes the need for cancer metabolism inhibitor thorough sensitivity analyses using a variety of appropriate statistical methods whenever possible. Here, the use of an exact method, which is likely more appropriate because of the limited number of studies, shows no statistically significant difference between the two drugs; this result directly contradicts the findings of Awad et al.1 Aside from the biases resulting from the reliance on large sample properties when statistical analyses of small

samples are being performed, current meta-analyses often reduce a complicated, multitrial meta-analysis to a single parameter from which absolute conclusions are drawn. A number of recent articles, including ones by Wang et al.7 and Cai et al.,8, 9 present a method that, applied to the issue of peginterferon alfa-2a versus peginterferon alfa-2b, would provide clinicians with clearer guidance about which product is most likely to be an appropriate treatment for any given patient. Pierre Crémieux Ph.D.*, * Analysis Group, Inc., Boston, MA. “
“To selleck chemical the Editor: Primary biliary cirrhosis (PBC) is considered to be an autoimmune disorder. When not adequately responding to medical treatment, PBC often progresses to liver cirrhosis, necessitating liver transplantation.[1] This constitutes a need for the development of animal models, both to unravel pathogenetic pathways and to test innovative therapeutic agents. Gershwin and his group have greatly contributed to this endeavor and in their most recent and intriguing manuscript successfully test a novel therapeutic approach in a well-established PBC model.

The largest trial5 alone represented nearly 70% of observations. Based on that trial, past research has shown no difference between peginterferon alfa-2a and peginterferon alfa-2b with respect to SVR. This underlines the importance of sensitivity analyses for examining the robustness of Awad et al.’s conclusions. Because the authors showed that there was no evidence of heterogeneity (I2 = 0) among the eight studies that they included, a fixed effects model

approach is appropriate. I applied a fixed effects exact inference procedure (proposed by Tian et al.6) as a sensitivity analysis to the data shown in Fig. 2 of Awad et al.’s article. This method is unbiased even for selleck chemicals small samples or when only a small number of studies are included in the meta-analysis. This robust method yielded a 95% confidence interval for

the risk ratio of 0.988-1.214, which included the null value of 1. A similar analysis limited to the approved starting dose of 1.5 μg/kg/week (which excluded 1016 of the 3070 patients in the IDEAL trial) also showed a lack of a statistically significant difference with an exact 95% confidence interval of 0.967-1.214. The discrepancy between the findings based on large sample methods and those based on exact methods emphasizes the need for Selleck ABT263 thorough sensitivity analyses using a variety of appropriate statistical methods whenever possible. Here, the use of an exact method, which is likely more appropriate because of the limited number of studies, shows no statistically significant difference between the two drugs; this result directly contradicts the findings of Awad et al.1 Aside from the biases resulting from the reliance on large sample properties when statistical analyses of small

samples are being performed, current meta-analyses often reduce a complicated, multitrial meta-analysis to a single parameter from which absolute conclusions are drawn. A number of recent articles, including ones by Wang et al.7 and Cai et al.,8, 9 present a method that, applied to the issue of peginterferon alfa-2a versus peginterferon alfa-2b, would provide clinicians with clearer guidance about which product is most likely to be an appropriate treatment for any given patient. Pierre Crémieux Ph.D.*, * Analysis Group, Inc., Boston, MA. “
“To selleck chemical the Editor: Primary biliary cirrhosis (PBC) is considered to be an autoimmune disorder. When not adequately responding to medical treatment, PBC often progresses to liver cirrhosis, necessitating liver transplantation.[1] This constitutes a need for the development of animal models, both to unravel pathogenetic pathways and to test innovative therapeutic agents. Gershwin and his group have greatly contributed to this endeavor and in their most recent and intriguing manuscript successfully test a novel therapeutic approach in a well-established PBC model.

To determine if miR-125b has a direct effect on cholangiocytes, we silenced miR-125b expression in vitro using a miR-125b inhibitor and measured proliferation by MTT assay, histamine secretion by EIA and VEGF-A expression by real-time PCR. Results: We found by both CK-19 and PCNA IHC, a progressive pattern of increased IBDM and cholangiocyte proliferation that MK-8669 nmr peaked at 6-8 weeks followed by a steady decline from 10-36 weeks of age with proliferation returning to levels of WT mice at 36 weeks. The gene expression pattern of CK-19, PCNA, HDC and VEGF-A

was similar to proliferation data, whereas the pattern of apoptosis demonstrated an opposite trend. Similar to the BDL model, miR-125b expression was decreased at peak proliferative weeks. In vitro, we found that inhibition of miR-125b expression increased proliferation, histamine secretion and VEGF-A expression. Conclusion: Our results demonstrate that there is a progressive pattern of proliferation followed by bile duct loss in MDR2−/− mice beginning at 1 week of age through 36 weeks of age. Similar to BDL-induced liver injury, the miR-125b/HDC/HA/VEGF axis regulates biliary proliferation in this model of PSC. Targeting this axis may be a potential therapeutic avenue for PSC. The MDR2−/− mouse may be an effective model to study molecular

and pathological mechanisms of PSC. Disclosures: The following people have nothing to disclose: Yuyan Han, Laura Hargrove, Lindsey Kennedy, Allyson B. Graf, Sharon DeMorrow, Fanyin Meng, Quy P. Nguyen, Victoria Huynh, Heather L. Francis Introduction: Primary sclerosing cholangitis (PSC) is a chronic, check details idiopathic, incurable cholangiopathy in which the pathogenesis remains obscure, in part because of the lack of appropriate experimental models. Here, through cellular,

molecular, and next-generation sequencing (NGS) methods, we describe the development of a PSC patient-derived cholangiocyte cell line and characterization of the phenotypic and signaling features. Methods: selleck We isolated cholangiocytes from stage 4 PSC patient liver explants by dissection, differential filtration, and immune-magnetic bead separation. We maintained cholangiocytes in culture and assessed for: i) cholangiocyte, cell adhesion, and inflammatory markers; ii) proliferation rate; iii) transepithelial electrical resistance (TEER); iv) cellular senescence; and v) transcriptomic profiles by NGS. We used two well-established normal human cholangiocyte cell lines (H69 and NHC) for comparison. Results: Isolated PSC cells expressed cholangiocyte (e.g. cytokeratin 7 and 19) and epithelial cell adhesion markers (EPCAM, ICAM) and were negative for hepatocyte and myofibroblast markers (albumin, α-actin). Proliferation rate was lower for PSC compared to normal cholangiocytes (4 vs. 2 days, respectively, p<0.01). Maximum TEER was also lower in PSC compared to normal cholangiocytes (100 vs. 145 Ωcm2, p<0.05).

Here, it is of interest that an HBV receptor called NTCP (sodium taurocholate cotransporting polypeptide) with interaction with the pre-S1 domain has recently been identified, and human and cynomolgus monkey NTCP have differences that could require the adaptation of human HBV to

be able to infect monkeys.[17] Although natural HBV infection in adult humans MG-132 ic50 is cleared in most cases, associated with vigorous host T-cell responses and liver inflammation, it has not yet been possible to develop treatment strategies that efficiently eliminate HBV infection. The current approaches with nucleos(t)ide analogs tenofovir and entecavir and/or PEG-IFN-α do not directly target the nonreplicating and stable form of nuclear HBV DNA, covalently closed circular DNA (cccDNA). HBV cccDNA is the template for viral RNA transcription, and to cure HBV, this form of HBV DNA must eventually be eliminated. Therefore, efforts are ongoing to develop drugs that prevent RNA transcription, for example, by applying HBV cccDNA-targeted enzymes, such as zinc-finger nucleases, inducing double-strand DNA breaks. Because these DNA breaks are not efficiently repaired, the thought is that this will lead to inactivation of viral genes and prevent HBV replication.[18, 19] Preliminary investigations could be performed PKC412 molecular weight with animal variants of HBV.[20]

However, the study of these novel HBV drugs will eventually require animal models of human hepatitis B for testing of safety

and efficacy. In conclusion, given the lack of suitable and readily available animal models for persistent human HBV infection, it would be a major breakthrough if chronic HBV infection in Old World monkeys can be developed, based on the unique adapted HBV strain identified by Dupinay et al. in M. fascicularis.[15] Old World monkeys are immunologically closely related to humans, and HBV-infected monkeys could thus be used to examine drugs designed to stimulate the immunity of chronically infected individuals or to directly target the cccDNA template in attempts to cure chronic HBV. However, it remains learn more to be determined whether the generation of persistent experimental infections can be achieved in Old World monkeys. Thus, additional studies will be required to confirm the utility of this model in experimental studies of chronic human HBV infection. Jens Bukh, M.D.1,2 “
“Aim:  To evaluate the efficacy of natural human interferon (IFN)-β and ribavirin in elderly patients infected with hepatitis C virus (HCV) genotype 2 and high virus load. Methods:  Inclusion criteria were age of 65 years or older, HCV genotype 2 and serum HCV RNA level of 5.0 logIU/mL or more. A total of 33 were enrolled in this retrospective cohort study. IFN-β was administrated i.v. at a dose of 6 million units daily for 4 weeks initially, followed by three times a week for 20 weeks. Ribavirin was given daily for 24 weeks at the dose described based on bodyweight.

Self-reported symptoms, such as reduced appetite, abdominal distention, and fatigue, were recorded and compared over the 1-4 weeks after transplantation. ALT, ALB, and TBIL levels and PT and MELD scores were compared from 1 to 4 weeks after transplantation in all patients. In regards to the long-term therapeutic effects and prognosis, ALT, ALB, and TBIL levels and PT and MELD scores were compared up to 48 weeks after transplantation. At 48 weeks after transplantation, only 6 and

26 patients in groups A and B returned to our hospital for follow-up, and their liver function indices were recorded. Only 15 of the Mitomycin C solubility dmso 26 patients in group B had matched baseline indices with the six patients in group A, and their liver functions indices were thus compared up to 48 weeks after transplantation. To evaluate long-term prognosis, the incidence of HCC and survival rates were recorded every 12 weeks after transplantation. Data of clinical and biochemical features were expressed as mean ± standard deviation and compared BIBW2992 using the chi-square and t tests. Analysis of long-term turnover were studied by survival analysis, from which the product-limit estimate was used to calculate the rates (i.e., HCC incidence and mortality), and the Kaplan-Meier curve was delineated. All data were analyzed by SPSS 13.0 software (SPSS Inc., Chicago, IL) and a value of P < 0.05 was considered statistically

significant. All MMSCs demonstrated a fusiform shape with a high karyoplasmic ratio and were integrated

into stable colonies, such as collagenoblasts (Fig. 1A,B). Flow cytometry analysis showed that MMSCs (third passage) from patients with liver failure this website caused by hepatitis B were positive for CD44 and negative for CD34 and CD45, which was consistent with that of healthy adults (Fig. 1C). The collection, separation, and transfusion of MMSCs were successful in all 53 patients, with a success rate of 100%. No serious side effects or complications (including hemorrhage, fever, infection, hepatalgia, etc.) were observed after transplantation. Four weeks after transplantation, patients had improved self-reported symptoms, compared with controls, but this difference was not significant. In the two groups, there were 35 and 68 patients who experienced increased appetite (P = 0.874), 33 and 59 patients experienced abdominal distension improvements (P = 0.465), and 35 and 61 patients experienced fatigue improvements (P = 0.334), respectively. Liver function comparisons at 1-4 weeks after transplantation indicated that there were no marked differences in ALT levels between the two groups (Table 2). Furthermore, in both groups, there were no dramatic differences in ALT levels between the cirrhosis and noncirrhosis subgroups (Table 3). ALB and TBIL levels of patients in group A were significantly superior to those in group B at week 2 after transplantation (Table 2; Fig. 2A,B).

The aim of this study is to investigate whether zinc sulfate therapy will result in improvement in clinical parameters and mechanistic biomarkers of AC. Methods: Subjects with Child-Pugh class A-B alcoholic cirrhosis were randomized to placebo or zinc sulfate 220 mg daily in the single center, NIH-funded, double-blind, placebo-controlled ZAC clinical trial. The 2 year study is ongoing. Here, baseline and 3 month data are presented including clinical parameters and serologic biomarkers of intestinal permeability and hepatic fibrosis. 10 non-drinking, age-matched, healthy controls (HC) were recruited as controls for baseline biomarker comparison.

Serologic biomarkers were measured by ELISA, and differences between means were determined by t-test.

Results: 22 AC subjects were randomized to placebo (n=10) or zinc (n=12) groups. Demographic variables were similar ABT-263 manufacturer between groups. However, the zinc group had more active drinkers than the placebo group (6 vs. 1). At baseline, the combined AC subjects (n=22) had a mean age of 54.0±10.1; a mean BMI of 27.2±3.3; a mean Child-Pugh score of 7.0±1.4; and a mean MELD score of 9.0±2.3. When Cisplatin compared to HC, AC had significantly decreased serum calprotectin. While serum LPS binding protein (LBP) tended to be lower in AC, serum soluble CD14 (sCD14) was significantly different. Serum hyaluronic acid (HA) was significantly increased in AC. There were trends towards increased serum tissue inhibitor of metalloproteinase-1 (TIMP-1) and decreased serum procollagen III N-terminal pro-peptide (P3NP) in AC. After three months of treatment, Child-Pugh and MELD scores tended to decrease in the zinc arm and increase in placebo arm. Serum calprotectin tended to decrease in zinc group, and increase in placebo group. Serum LBP and sCD14 were not significantly changed by zinc therapy. Serum TIMP-1 was significantly increased in AC patients

treated with placebo (p=0.032), whereas this increase was prevented by zinc therapy. Serum hyaluronic acid (HA) level tended to decrease in zinc group, but not in the placebo group. find more Serum P3NP tended to increase in placebo group but not in the zinc group. Conclusion: This 3 month interim analysis of the ongoing 2 year ZAC clinical trial suggests that zinc sulfate may attenuate fibrosis in alcoholic cirrhosis. Longer term follow up is required to determine if zinc improves clinical outcomes in AC. Disclosures: Craig J. McClain – Consulting: Vertex, Gilead, Baxter, Celgene, Nestle, Danisco, Abbott, Genentech; Grant/Research Support: Ocera, Merck, Glaxo SmithKline; Speaking and Teaching: Roche The following people have nothing to disclose: Ming Song, Mohammad K. Mohammad, Keith C. Falkner, Matthew C. Cave Objective: In a previous publication, we reported that when compared to a moderate fat diet and ethanol, the addition of a high fat diet and ethanol resulted in differential regulation of adiponectin/AMPK signaling in C57Bl/6J mice (Shearn et al. JNB 2013).

The aim of this study is to investigate whether zinc sulfate therapy will result in improvement in clinical parameters and mechanistic biomarkers of AC. Methods: Subjects with Child-Pugh class A-B alcoholic cirrhosis were randomized to placebo or zinc sulfate 220 mg daily in the single center, NIH-funded, double-blind, placebo-controlled ZAC clinical trial. The 2 year study is ongoing. Here, baseline and 3 month data are presented including clinical parameters and serologic biomarkers of intestinal permeability and hepatic fibrosis. 10 non-drinking, age-matched, healthy controls (HC) were recruited as controls for baseline biomarker comparison.

Serologic biomarkers were measured by ELISA, and differences between means were determined by t-test.

Results: 22 AC subjects were randomized to placebo (n=10) or zinc (n=12) groups. Demographic variables were similar check details between groups. However, the zinc group had more active drinkers than the placebo group (6 vs. 1). At baseline, the combined AC subjects (n=22) had a mean age of 54.0±10.1; a mean BMI of 27.2±3.3; a mean Child-Pugh score of 7.0±1.4; and a mean MELD score of 9.0±2.3. When buy PCI-32765 compared to HC, AC had significantly decreased serum calprotectin. While serum LPS binding protein (LBP) tended to be lower in AC, serum soluble CD14 (sCD14) was significantly different. Serum hyaluronic acid (HA) was significantly increased in AC. There were trends towards increased serum tissue inhibitor of metalloproteinase-1 (TIMP-1) and decreased serum procollagen III N-terminal pro-peptide (P3NP) in AC. After three months of treatment, Child-Pugh and MELD scores tended to decrease in the zinc arm and increase in placebo arm. Serum calprotectin tended to decrease in zinc group, and increase in placebo group. Serum LBP and sCD14 were not significantly changed by zinc therapy. Serum TIMP-1 was significantly increased in AC patients

treated with placebo (p=0.032), whereas this increase was prevented by zinc therapy. Serum hyaluronic acid (HA) level tended to decrease in zinc group, but not in the placebo group. click here Serum P3NP tended to increase in placebo group but not in the zinc group. Conclusion: This 3 month interim analysis of the ongoing 2 year ZAC clinical trial suggests that zinc sulfate may attenuate fibrosis in alcoholic cirrhosis. Longer term follow up is required to determine if zinc improves clinical outcomes in AC. Disclosures: Craig J. McClain – Consulting: Vertex, Gilead, Baxter, Celgene, Nestle, Danisco, Abbott, Genentech; Grant/Research Support: Ocera, Merck, Glaxo SmithKline; Speaking and Teaching: Roche The following people have nothing to disclose: Ming Song, Mohammad K. Mohammad, Keith C. Falkner, Matthew C. Cave Objective: In a previous publication, we reported that when compared to a moderate fat diet and ethanol, the addition of a high fat diet and ethanol resulted in differential regulation of adiponectin/AMPK signaling in C57Bl/6J mice (Shearn et al. JNB 2013).

This approach has advantages: the resulting model is immunocompetent and can be bred, and specific knowledge of restriction factors is not required. The resistance of mice to HCV is multifactorial and at least is determined by blocks in viral entry and

replication (Fig. 1A).7, 8 HCV entry is a complex process facilitated by four essential membrane proteins: scavenger receptor Dasatinib chemical structure class B type 1 (SCARB1), which is also known as SR-BI; CD81; claudin 1 (CLDN1); and OCLN.7, 11-13 Comparisons of the human and mouse orthologues reveal that, although mouse SCARB1 and mouse CLDN1 support HCV entry similarly to their human homologues, mouse CD81 (mCD81) and mouse OCLN do not (Fig. 1B).7 In their recent work, Bitzegeio et al.14 make an important first step toward developing a murine tropic virus. Using an unbiased selection approach, the authors

adapted a laboratory strain of HCV allowing to use BGB324 cost a mouse entry factor. Taking advantage of the high mutational plasticity of HCV, Bitzegeio et al. identified three adaptive mutations in viral glycoproteins E1 and E2 that allowed the virus to enter cells expressing human SCARB1, human CLDN1, human OCLN, and mCD81. Interestingly, both mutations in E2 are located in hypervariable region 1, which is thought to be dispensable for CD81 binding. These mutations strikingly increased the affinity of the virus for the large extracellular loop of hCD81, and this suggested an indirect enhancement by the exposure of a CD81 binding site. Moreover, the mCD81-adapted virus permitted entry via rat and hamster orthologues. In addition to modifying CD81 tropism, the adaptive mutations altered the usage of human SCARB1 and human OCLN. Blocking antibodies against human SCARB1 and silencing of human OCLN had a less pronounced effect on the entry of the mutant virus versus the parental strain, and this suggested that the mCD81-adapted virus was less dependent on SCARB1 and OCLN. In addition, mouse

fibroblasts expressing all four murine entry factors supported the uptake of adapted virus, and this entry could be blocked with anti-mCD81 antibodies; this selleck kinase inhibitor indicated that the species restriction to human OCLN was altered, whereas CD81 dependence was maintained. Structural changes in the murine-adapted E1/E2 complex were evident because affinities for neutralizing antibodies targeting conformational epitopes were drastically altered. Increased fusogenic activity of the mutant E1/E2 complex indicated that the adapted proteins might adopt a structure resembling that acquired during receptor interactions. It has previously been demonstrated that HCV requires not only a low pH shift but also additional primers for efficient membrane fusion.15 The latter requirement appears to be less stringent in the adapted glycoprotein complex, as measured by temperature shift assays.

1, 2 First studied in patients with hepatitis C,3, see more 4 TE has now been validated in populations with various liver disorders and the technology has gained widespread use in many regions.5, 6 The diagnostic performance of TE is excellent for cirrhosis and moderate for significant fibrosis.5, 7, 8 Advantages of TE include its simplicity, short performance time, immediate results, patient acceptance, and ease

of incorporation into an outpatient clinical setting. A disadvantage of TE is the inability to accurately assess liver stiffness in some patients, predominantly due to obesity. Because subcutaneous fat attenuates the transmission of shear waves into the liver and the ultrasonic signals used to measure their speed of propagation, FibroScan failure (i.e., no valid measurements) and unreliable results occur in ≈3%-5% and 10%-15% of patients, Pembrolizumab price respectively.6, 9-13 Numerous studies have shown that obesity, defined as a body mass index (BMI) ≥30 kg/m2, is the strongest predictor of failed or unreliable liver stiffness measurement (LSM).6, 9, 12, 13 Moreover,

subcutaneous adipose tissue may lead to overestimation of liver stiffness. Due to the rising prevalence of obesity and associated nonalcoholic fatty liver disease (NAFLD),14 this limitation is a potentially important barrier to the effective use of TE in clinical practice. To mitigate this limitation, a new FibroScan probe—designated the “XL” probe—has been designed specifically for use in obese patients. The XL probe differs from the standard M probe by its utilization of a lower frequency and more sensitive ultrasonic transducer, a deeper focal length, selleck products a larger vibration amplitude, and a greater depth of measurement below the skin surface. Preliminary data suggest that the XL probe improves the feasibility of LSM in obese patients; however, histological data confirming its diagnostic accuracy are limited.15, 16 The objectives of this prospective, multicenter study were to compare the feasibility and reliability of the XL and M probes for LSM

in overweight and obese patients with various liver disorders. In addition, the diagnostic accuracy of the two probes was compared using liver biopsy as the reference standard. AUROC, area under the receiver operating characteristic curve; CI, confidence interval; IQR, interquartile range; IQR/M, IQR over the median; LSM, liver stiffness measurement; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD Activity Score; OR, odds ratio; TE, transient elastography. In this prospective study, adults (≥18 years) with chronic liver disease of any etiology and a BMI ≥28 kg/m2 who had undergone percutaneous liver biopsy within 6 months, or were scheduled to undergo biopsy within 1 month, were eligible.