Fibrosis Stage In Patients Research Articles

Association of serum autotaxin levels with liver fibrosis in patients pretreatment and posttreatment with chronic hepatitis C.

The evaluation of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection is important as it is a risk factor for hepatocellular carcinoma. In the recent years, autotaxin (ATX) has been established as a new noninvasive biomarker to predict liver fibrosis. However, antiviral treatment has been reported to decrease serum ATX, but it is unclear whether posttreatment ATX levels reflect liver fibrosis. In the present study, the correlation between ATX and liver fibrosis in pretreatment and posttreatment patients with HCV infection was analyzed. A total of 199 samples from 136 patients with HCV infection who had undergone hepatic biopsy before and/or after antiviral treatment at Osaka City University Hospital were used. Posttreatment patients included 38 interferon-treated patients and 80 interferon-free direct-acting antiviral-treated patients; all patients achieved a sustained virological response (SVR). Serum ATX levels were determined by enzyme immunoassay with an AIA-2000 analyzer. Serum ATX levels were largely correlated with liver fibrosis stage in patients with HCV infection before and after antiviral treatment. The measured values decreased even in similar liver fibrosis stages after treatment. The area under the receiver operating characteristic curve for the ability of ATX to diagnose above F2 stage before treatment was 0.81 (both male and female) and that after achieving SVR, it was 0.71 (male) and 0.72 (female). Serum ATX levels were correlated with histological liver fibrosis stage after achieving SVR. However, separate cutoff values before and after antiviral therapy should be established.

Comparison of serum fibrosis biomarkers for diagnosing significant liver fibrosis in patients with chronic hepatitis B.

Chronic hepatitis B (CHB) virus continues to be a leading cause of morbidity and mortality worldwide. The diagnosis of liver fibrosis has a key role in selecting patients with CHB for antiviral treatment. However, serum biomarkers demonstrate limited diagnostic utility. The present study aimed to compare the performances of fibrosis biomarkers for diagnosing significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB and to identify the most appropriate biomarker for these patients. The current study included 96 antiviral-naïve patients with CHB who underwent liver biopsy. METAVIR scoring system was used to assess liver fibrosis and necroinflammation. The diagnostic performances were evaluated of the platelet (PLT) count; the levels of hyaluronan, serum 7S domain of type 4 collagen, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer (M2BPGi) and N-terminal type III collagen propeptide (Pro-C3); the fibrosis index based on four factors; the aspartate aminotransferase-to-platelet ratio index; and enhanced liver fibrosis score for identifying significant liver fibrosis [≥fibrosis stage 2 (F2)]. All fibrosis biomarkers, except the Pro-C3 level, correlated with the fibrosis stage. M2BPGi was better than other biomarkers for diagnosing ≥F2, with the highest area under the curve of 0.902. M2BPGi demonstrated a higher diagnostic accuracy for significant fibrosis than mild/severe fibrosis or cirrhosis. However, no significant correlation was observed between the M2BPGi level and fibrosis stage in patients with CHB having significant liver necroinflammation defined as ≥ necroinflammatory activity 2. The M2BPGi level and PLT count were exclusively correlated with the fibrosis stage in 73 patients without significant liver necroinflammation. M2BPGi demonstrated the highest diagnostic performance for significant fibrosis in patients having significant liver fibrosis with no significant liver necroinflammation. In conclusion, the M2BPGi level can accurately diagnose significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB.

Serum hepcidin levels are related to serum markers for iron metabolism and fibrosis stage in patients with chronic hepatitis B: A cross-sectional study

Background and study aimsThe clinical significance of serum parameters of iron metabolism and hepcidin in liver disease remains unknown. Therefore, this study aimed to evaluate the association of serum hepcidin levels with fibrosis stage and serum iron parameters in patients with chronic hepatitis B (CHB). Patients and MethodsThis cross-sectional study included 126 treatment-naïve patients with CHB (median age, 39.0 years; 64.3% males) who were positive for hepatitis B surface antigen and 23 healthy controls (median age, 33.0 years; 52.2% males). Data on patient demographics, serum hepcidin levels, liver function tests and serum iron parameters and liver biopsy findings including fibrosis grade, histological activity index (HAI) and liver iron level were recorded. ResultsThe median (minimum–maximum) serum hepcidin levels were significantly lower in the CHB group than in the control group [71.2 (13.3–672.7) vs. 657.5 (201.7–2714.2) pg/mL, p < 0.001]. Higher fibrosis stage was associated with higher transferrin saturation (p = 0.029), serum ferritin level (p < 0.001) and viral load (p < 0.001). Fibrosis stage and HAI were positively correlated with ferritin (r = 0.407, p < 0.001 and r = 0.415, p < 0.001, respectively) and transferrin saturation (r = 0.219, p = 0.026 and r = 0.290, p = 0.003, respectively) levels, whereas hepcidin level was negatively correlated with fibrosis stage (r = −0.175, p = 0.051), viral load (r = −0.209, p = 0.020) and ferritin level (r = −0.244, p = 0.006) level. There were no significant differences in serum iron level, total iron binding capacity and liver iron level among patients with different stages of fibrosis. ConclusionReduced hepcidin levels and elevated transferrin saturation and ferritin levels are linked to fibrosis severity and HAI in patients with CHB.

Liver stiffness as measured by two-dimensional shear wave elastography overestimates the stage of fibrosis in patients with chronic hepatitis B and hepatic steatosis

Two-dimensional shear wave elastography (2D-SWE) is a non-invasive technique for measuring liver stiffness (LS) and is used to assess the degree of hepatic fibrosis in patients with chronic hepatitis B (CHB). Despite its usefulness, several factors, other than hepatic fibrosis, can affect its diagnostic accuracy. Hepatic steatosis (HS) is a common lesion in CHB that has increasingly been getting attention in the field of disease development; however, its influence on the measurement of LS remains unclear. We aimed to determine whether HS affects the diagnostic accuracy of 2D-SWE in patients with CHB. Serum parameters and LS values were obtained from 161 patients with CHB. The degrees of hepatic fibrosis and inflammatory activity were estimated based on the METAVIR Cooperative Study Group criteria, and the extent of HS was defined as the percentage of hepatocytes containing fat droplets using oil red staining. We found that LS values were independently correlated with HS in the early stages of hepatic fibrosis (F0-F2 or F0-3). Furthermore, LS values in patients with significant steatosis (S≥10%) were higher than the counterpart in fibrosis stages F0-2 (6.82±1.57 vs. 7.92±1.99; p=0.010) and F0-3 (7.18±1.84 vs. 8.25±1.91; p=0.007). Therefore, false positive rates (FPRs) in the diagnosis of advanced fibrosis (16.00% vs. 37.04%, p=0.037) and cirrhosis (6.67% vs. 21.62%, p=0.030) were higher in patients with significant steatosis. In conclusion, the use of 2D-SWE in the measurement of LS overestimates the stage of hepatic fibrosis in CHB patients with HS>10%. This should be taken into consideration to combine LS results with other non-invasive parameters to improve its accuracy.

Magnetic resonance elastography in staging liver fibrosis in non-alcoholic fatty liver disease: a pooled analysis of the diagnostic accuracy

BackgroundThis study was performed to systematically evaluate the accuracy of magnetic resonance elastography (MRE) in staging of liver fibrosis in non-alcoholic fatty liver disease (NAFLD).MethodsPUBMED, EMBASE, Web of Science, CNKI, Cochrane Library database were searched from January 2008 to December 2018 for studies related to MRE in the diagnosis of NAFLD liver fibrosis. The quality of the included literature was assessed by Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The pooled sensitivity, the pooled specificity, and area under the receiver operating characteristic curve (AUROC) value was performed by STATA 14.0 software.ResultsA total of 12 studies were included, involving 910 patients. The pooled sensitivity and specificity of each group were 0.77 (95%CI 0.69–0.83) and 0.90 (95%CI 0.83–0.94) for F ≥ 1 (mild liver fibrosis), 0.87 (95%CI 0.74–0.94) and 0.86 (95%CI 0.71–0.94) for F ≥ 2 (significant liver fibrosis), 0.89 (95%CI 0.81–0.94) and 0.84 (95%CI 0.63–0.94) for F ≥ 3(severe liver fibrosis), 0.94 (95%CI 0.85–0.98) and 0.75 (95%CI 0.35–0.94) for F ≥ 4 (early cirrhosis), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.89, 0.93, 0.93, and 0.95, respectively.ConclusionsMRE has high accuracy in the diagnosis of hepatic fibrosis staging in patients with NAFLD.

Impact of laparoscopic sleeve gastrectomy on fibrosis stage in patients with child-A NASH-related cirrhosis.

Bariatric surgery can improve non-alcoholic fatty liver disease (NAFLD). Yet data on the effect on fibrosis are insufficient and controversial. This work endeavored to evaluate the safety of laparoscopic sleeve gastrectomy (LSG) in cases that have compensated non-alcoholic steatohepatitis (NASH)-related cirrhosis and its impact on fibrosis stage. The current prospective work involved 132 cases with Child-A NASH-related cirrhosis suffering from morbid obesity scheduled for LSG. They were subjected to preoperative assessment, wedge biopsy, and ultrasound-guided true-cut liver biopsy after 30months. Patients were included if proved to have F4 fibrosis initially. The liver condition was assessed based on the NALFD Activity Score (NAS). The primary outcome measure was the impact of LSG on fibrosis stage and its relation to weight loss. The analysis included only 71 patients who completed the 30-month follow-up period. By the end of the follow-up interval, there was a substantial weight loss with a reasonable resolution of comorbidities. The median NAS decreased significantly from 6 (1-8) to 3 (0-6) after surgery. Fibrosis score regressed to F2 in 19 patients (26.8%) and F3 in 29 (40.8%). Patients with improved scores had a significantly higher amount of weight loss (p < 0.001). Improvement was more frequent in males (p = 0.007). By 30months after treatment, 53.8% of cases with borderline NASH and 36.8% of those with probable NASH showed complete resolution, and 44.7% of patients with NASH showed improvement. Steatosis improved in 74.6% of patients (p < 0.001). In patients with NASH-related liver cirrhosis of Child class A, LSG may be a secure approach for the management of morbid obesity. It has a long-term benefit for both obesity and liver condition with significant improvement of steatosis, steatohepatitis, and fibrosis.

The Importance of Transaminases Flare in Liver Elastography: Characterization of the Probability of Liver Fibrosis Overestimation by Hepatitis C Virus-Induced Cytolysis.

Background: Liver stiffness measurement (LSM) is crucial for appropriate fibrosis staging in patients with ongoing hepatitis C virus (HCV) infection. However, there is still an ongoing debate on the impact of serum transaminases (aspartate-aminotransferase, AST; alanine-aminotransferase, ALT) on LSM. Methods: We selected 110 patients undergoing HCV eradication therapy with LSM compatible with significant liver fibrosis. LSM was evaluated prior to therapy and one year after HCV eradication. Results: LSM showed a median decrease of 35% from baseline values, and 67 (61%) patients showed posttreatment values compatible with lower fibrosis stages. We developed two logistic regression models to determine the probability of liver fibrosis overestimation according to serum transaminase. The probability of overestimation of two or more fibrosis grade is equal to (1) 50% for AST of 99 IU/L (2.2 ULN) and ALT of 90.5 IU/L (2 ULN), (2) 80% for AST of 123.5 IU/L (2.74 ULN) and ALT of 101.5 IU/L (2.25 ULN), and (3) reaches 100% for AST of 211 IU/L (4.7 ULN) and ALT of 140 IU/L (3.1 ULN). Conclusions: This study highlights the impact of serum transaminases on LSM. We believe that our findings may serve as a reference point for appropriate fibrosis stratification by liver elastography in patients with HCV infection.

Pentraxin-3 is not related to disease severity in cirrhosis and hepatocellular carcinoma patients

The acute-phase protein pentraxin-3 (PTX3) is a component of the innate immune system. Inflammation and tissue injury increased PTX3 in the injured liver, and accordingly, circulating PTX3 was induced in patients with chronic liver diseases. In the present study, PTX3 protein was determined in systemic, hepatic, and portal vein plasma of patients with liver cirrhosis to assess a possible association between hepatic PTX3 release and extent of liver injury. However, PTX3 levels were not related to disease severity. Of note, portal PTX3 levels were higher than concentrations in the hepatic vein. PTX3 in the hepatic and portal veins was negatively correlated with factor V, antithrombin 3, and prothrombin time. PTX3 did neither correlate with C-reactive protein nor galectin-3 or resistin, whereby the latter two proteins are associated with hepatic injury. PTX3 levels were not changed in cirrhosis patients with ascites or varices and did not correlate with the hepatic venous pressure gradient. Likewise, serum PTX3 was not correlated with histological steatosis, inflammation, or fibrosis stage in patients with hepatocellular carcinoma (HCC). Moreover, PTX3 was not associated with tumor node metastasis classification in HCC. Above all, PTX3 increased in hepatic, portal, and systemic blood immediately after transjugular intrahepatic portosystemic shunt (TIPS). Higher PTX3 in portal than hepatic vein plasma and further increase after TIPS suggests that the liver eliminates PTX3 from the circulation. In summary, PTX3 is not of diagnostic value in cirrhosis and HCC patients.

Corrected integrated density: a novel method for liver elastic fibers quantification in chronic hepatitis C

BackgroundElastic fibers deposition is triggered during liver fibrosis and is related to worse clinical prognosis in chronic hepatitis C patients. This study aimed to verify if a new method for elastic fiber quantification can be used to discriminate between different degrees of fibrosis in liver biopsies of patients with hepatitis C.MethodsIndividuals presenting with different degrees of fibrosis in liver biopsy were included. Slides of liver samples were stained with orcein with and without prior oxidation. Morphometric analysis was proceeded, and quantification accomplished by corrected integrated density.ResultsTwenty-seven patients, mean age 52 years-old, 59% women, were included. Elastic fibers density was higher in advanced fibrosis patients and there was a positive correlation with Metavir score (Spearman r = 0.609, p < 0.001), as well as with the noninvasive scores Fib-4 (Pearson r = 0.46, p = 0.029) and APRI (r = 0.52, p = 0.01).ConclusionMorphometric analysis by corrected integrated density demonstrates that elastic fibers abundance is higher in advanced stage of fibrosis in patients with hepatitis C.

Association Between Fibrosis Stage and Outcomes of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint. We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years). Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplant RR, 5.42 (95% CI, 1.05-27.89); and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings. In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.

Liver stiffness measurement in non-alcoholic fatty liver disease: Two is better than one.

Repeating liver stiffness measurement (LSM) was recently reported to improve accuracy to diagnose fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD). There are to date no other studies confirming this finding. This aims to evaluate the accuracy of repeating LSM for the diagnosis of fibrosis stage in NAFLD patients. Retrospective analysis of prospectively collected data on adult NAFLD patients who had two FibroScan examination within 6months prior to liver biopsy. F3-F4 fibrosis was excluded using LSM cut-off of 7.9kPa. A total of 136 patients were recruited. Eighty-five percent (115/136) of patients had high baseline LSM (≥7.9kPa). Among them, 25% (29/115) had low repeat LSM (<7.9kPa), with only two patients having F3 fibrosis. Forty-eight percent (41/86) of patients with high baseline and repeat LSMs had greater than or equal to F3-F4 fibrosis. All 21 patients with low baseline LSM had F0-F2 fibrosis, except one patient with high repeat LSM who had F3 fibrosis. A strategy of repeating LSM, where only patients with high LSM on both baseline and repeat scans are considered for liver biopsy, will be able to reduce the number of patients being considered for liver biopsy from 85% to 63%. The sensitivity, specificity, positive predictive value, and negative predictive value based on only the baseline scan was 98%, 22%, 37%, and 95%, respectively, while based on the strategy of repeating LSM was 93%, 51%, 48%, and 94%, respectively. False positive diagnosis of advanced fibrosis in NAFLD patients can be reduced, and unnecessary liver biopsy can be avoided by repeating LSM.

Proteomic screening of plasma identifies potential noninvasive biomarkers associated with significant/advanced fibrosis in patients with nonalcoholic fatty liver disease.

Noninvasive biomarkers are clinically useful for evaluating liver fibrosis stage in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to compare plasma proteins in patients with early nonalcoholic steatohepatitis (NASH) (F0-F1) versus NASH with significant/advanced fibrosis (F2–F4) to determine whether candidate proteins could be used as potential noninvasive biomarkers. Nineteen biopsy-proven NAFLD patients including ten early NASH patients and nine NASH patients with significant/advanced fibrosis were enrolled in the present study. High-resolution proteomics screening of plasma was performed with the SCIEX TripleTOF 5600 System. Proteins were quantified using two different software platforms, Progenesis Qi and Scaffold Q+, respectively. Progenesis Qi analysis resulted in the discovery of 277 proteins compared with 235 proteins in Scaffold Q+. Five consensus proteins (i.e. Complement component C7; α-2-macroglobulin; Complement component C8 γ chain; Fibulin-1; α-1-antichymotrypsin) were identified. Complement component C7 was three-fold higher in the NASH group with significant/advanced fibrosis (F2–F4) compared with the early NASH (F0-F1) group (q-value = 3.6E-6). Complement component C7 and Fibulin-1 are positively correlated with liver stiffness (P=0.000, P=0.002, respectively); whereas, Complement component C8 γ chain is negatively correlated (P=0.009). High levels of Complement C7 are associated with NASH with significant/advanced fibrosis and Complement C7 is a perfect classifier of patients included in this pilot study. Further studies will be needed in a larger validation cohort to confirm the utility of complement proteins as biomarkers or mechanistic determinants of NASH with significant/advanced fibrosis.

The Alpha-1 Antitrypsin Polymer Load Correlates With Hepatocyte Senescence, Fibrosis Stage and Liver-Related Mortality.

Alpha-1 antitrypsin deficiency (AATD) is an important, inherited cause of chronic liver disease. Marked variation in fibrosis stages in patients with homozygous deficiency and those factors that determine whether heterozygous carriers develop liver fibrosis, remain unexplained. Murine studies implicate polymerized alpha-1 antitrypsin (AAT) within hepatocytes as pathogenic. The relationship between the quantity of polymerized AAT within hepatocytes (polymer load), stage of hepatic fibrosis and liver-related clinical outcomes (death, evolution to hepatocellular carcinoma, or need for liver transplantation) were investigated using liver tissue from 92 patients at first presentation with either homozygous or heterozygous AATD. Further tissue-based studies were undertaken to determine if polymerized AAT was associated with failure of cell cycle progression, accelerated aging or hepatocyte senescence by immunohistochemical analysis. The AAT polymer load correlated closely with hepatic fibrosis stage and long-term clinical outcome, independent of homozygous or heterozygous status. AAT polymers within hepatocytes correlated closely with failure of cell cycle progression assessed using cell cycle phase markers, accelerated aging manifest as shortened telomeres and other markers consistent with hepatocyte senescence manifest as the presence of nuclear p21 expression and enlarged nuclei. The proportion of p21 positive hepatocytes or hepatocytes with enlarged nuclei correlated with hepatic fibrosis stage and the long-term clinical outcome. These data suggest that accumulation of AAT polymers within hepatocytes drives senescence. Quantitation of both the AAT polymer load or hepatocyte senescence markers correlated with hepatic fibrosis stage and the long-term clinical outcome. Either or both could be considered markers of disease severity and treatment response in clinical trials.

Noninvasive inflammatory markers for assessing liver fibrosis stage in autoimmune hepatitis patients.

ObjectiveTo examine the accuracy of noninvasive inflammatory markers in predicting liver fibrosis stage in patients with autoimmune hepatitis (AIH).Patients and methodsWe enrolled 55 patients with AIH and 60 healthy controls in this study, and divided them into three groups: F0 (control); F1–F3 (noncirrhotic fibrosis); and F4 (cirrhosis). The following markers were analyzed for all participants: lymphocyte-to-neutrophil ratio (LNR); lymphocyte-to-platelet ratio (LPR); lymphocyte-to-monocyte ratio (LMR); immunoglobulin-to-platelet ratio (IGPR); aminotransferase-to-platelet ratio index (APRI); aspartate aminotransferase-to-alanine aminotransferase ratio (AAR); and fibrosis-4 score (FIB-4). The predictive accuracy of these noninvasive markers was assessed using area under the receiver operating characteristic curve. Multivariate ordinal logistic regression models were used to analyze associations between the noninvasive markers and liver fibrosis stage.ResultsAAR, LPR, LMR, IGPR, APRI, and FIB-4 were linked to liver fibrosis-stage (P < 0.05), with correlation indices of − 0.219, 0.258, − 0.149, 0.647, 0.841, and 0.704, respectively, but not LNR (P = 0.093). area under the receiver operating characteristic curves of LPR, IGPR, AAR, LMR, APRI, and FIB-4 for detecting cirrhosis (F4 vs. F0–F3) were 0.936 (95% confidence interval: 0.870–1.000, P < 0.001), 0.939 (0.875–1.000, P < 0.001), 0.528 (0.319–0.738, P = 0.768), 0.555 (0.409–0.700, P = 0.568), 0.798 (0.694–0.902, P = 0.002), and 0.881 (0.796–0.967, P < 0.001). Our multivariate ordinal regression analysis showed that LPR and IGPR were associated independently with liver fibrosis stage, with a coefficient of 0.385 (95% confidence interval: 0.103–0.667, P = 0.007) and 14.903 (2.091–27.786, P = 0.023), respectively.ConclusionLPR and IGPR were associated independently with liver fibrosis stage in treatment-naive AIH, and were superior to APRI and FIB-4 in detecting cirrhosis.

Predictive validation of qualitative fibrosis staging in patients with chronic hepatitis B on antiviral therapy

The fibrosis in chronic hepatitis shows dynamic changes during antiviral therapy (AVT). We investigated whether P-I-R (progressive vs. indeterminate vs. regressive) staging is predictive of hepatocellular carcinoma (HCC) recurrence in patients with chronic hepatitis B (CHB) taking AVT who underwent resection. Patients with CHB-related HCC who underwent curative resection between 2004 and 2017 and had received ≥2 years AVT at the time of resection were eligible. Two pathologists performed P-I-R staging. In total, 104 patients with CHB-related HCC were enrolled. The mean age of the study population was 56.3 years. The mean duration of AVT at the time of resection was 62.6 months. During the follow-up period (mean, 45.5 months), 20 (19.2%) and 14 (13.5%) patients developed early and late recurrence of HCC, respectively. The cumulative incidence of late recurrence was significantly lower in patients with regressive patterns than in those with indeterminate and progressive patterns according to P-I-R staging (P = 0.015, log-rank test), although the cumulative incidence of overall recurrence according to P-I-R staging was similar. Hepatitis B virus DNA levels (hazard ratio [HR] = 3.200, P = 0.020) and the regressive P-I-R staging pattern (HR = 0.127, P = 0.047) independently predicted the risk of late recurrence. One-time assessment of the P-I-R staging at the time of curative resection in patients with CHB-related HCC receiving AVT independently predicted late HCC recurrence. Therefore, qualitative fibrosis assessment by P-I-R staging might be useful in predicting the outcomes of patients with CHB undergoing AVT.

How intrahepatic cholestasis affects liver stiffness in patients with chronic hepatitis B: a study of 1197 patients with liver biopsy.

To evaluate the impact of intrahepatic cholestasis on liver fibrosis staging using liver stiffness measurements (LSM). Between July 2011 and September 2016, a total of 1197 patients with chronic hepatitis B (CHB) infection were enrolled to collect clinical, biological, 2D shear wave elastography (SWE), and histological (METAVIR scoring system) data. LSM was compared in patients with normal total bilirubin (TB) versus abnormal TB for each group of fibrosis stage, alanine aminotransferase (ALT) levels, and inflammation grade. Logistic regression and ROC analyses were performed to assess the benefit of adding TB and to LSM for fibrosis staging. Nine hundred and seventy-three patients were analyzed. Within the same fibrosis stage, LSMs showed significantly higher value in patients with abnormal TB than those with normal TB. Increased LSM for abnormal TB was generally found within different sub-groups of patients (≤ F2 or ≥ F3; ALT < 2 × upper limit of normal (ULN) or ALT ≥ 2 × ULN; METAVIR activity grade ≤ 1 or ≥ 2). Patients with abnormal TB level showed higher optimal cutoff values: 10.46kPa for ≥ F2, 10.94kPa for ≥ F3, and 15.88kPa for F4, than those with normal TB (7.62kPa, 8.26kPa, and 11.01kPa, respectively). LSM assessed fibrosis stage (≥ F2, ≥ F3, F4) showed higher false positive rate in patients with abnormal TB level (44.6%, 45.1%, 39.6%) than those with normal TB (20.7%, 17.1%, 14.4%). However, the area under the ROC curve did not change appreciably when adding TB to LSM for fibrosis stage. Intrahepatic cholestasis showed slight effect on LSM in patients with CHB, also leading to overestimation of liver fibrosis stages. But adding TB level to LSM did not improve the overall diagnostic performance of liver fibrosis stage. • Intrahepatic cholestasis showed slight effect on liver stiffness measurements (LSMs) in chronic HBV patients. • Patients with abnormal total bilirubin (TB) level showed higher optimal cutoff values and false positive rate. • When taking into account intrahepatic cholestasis, the diagnostic performance of LSM for liver fibrosis staging in patients with chronic HBV infection will not improve.

2184 The First Case of Endoscopic Ultrasound Guided Liver Biopsy Followed by Endoscopic Sleeve Gastroplasty in the Same Session

INTRODUCTION: Endoscopic sleeve gastroplasty (ESG) is a novel procedure that is safe and effective for weight loss that has been shown to have significantly less morbidity than alternative bariatric procedures. We present the first case of Endoscopic ultrasound-guided liver biopsy (EUS-LB) done in the same session as ESG. Both procedures were without complications, and were technically and clinically successful. CASE DESCRIPTION/METHODS: 28 year old female with hypertension and morbid obesity presented for elevated liver function tests concerning for NAFLD. In past 20 months patient went from 268 to 293 pounds and failed lifestyle interventions. Medications were Famotidine and Lipitor. Physical Exam was notable for obese female, increased waist circumference, nontender and non distended abdominal exam without rebound or guarding. CBC,BMP,PT/INR were within normal limits. Liver Function: AST 54 U/L, ALT 78U/L, Alkaline Phosphatase 56 U/L, Total Bilirubin 1.0 mg/dL. Ultrasound revealed hepatic steatosis, and FibroScan showed Fibrosis Score F4 consistent with cirrhosis. She did not have physical exam or lab findings consistent with cirrhosis. Patient was planned for ESG for weight loss and given Fibroscan results, same session EUS-LB was performed. EUS-LB was performed first in left lobe with 19 gauge FNB needle with no complications. ESG was performed successfully without complications. Upper GI series the next morning revealed no extravasation, patient tolerated diet and was discharged home. One month later, patient BMI decreased from 51kg/m2à45kg/m2, 298 to 263 lbs. No complaints of abdominal pain, nausea, vomiting and tolerating diet. Pathology from Liver Biopsy showed NAS Score 4/8 consistent with steatohepatitis, Stage 2-3 fibrosis. DISCUSSION: EUS-LB is an effective method for liver biopsy with minimal complications. ESG significantly reduces BMI with low morbidity . With the prevalence of NAFLD and subsequent conversion to NASH and cirrhosis increasing, non-invasive tests are utilized to stage fibrosis in patients with NASH. In cases where there is a discordance between clinical findings and Fibroscan results, liver biopsy can be obtained. This case demonstrates when a liver biopsy is indicated, EUS-LB is a safe and efficient option in a patient undergoing an endoscopy for other reasons. This is also the first reported case of EUS-LB and ESG in the same session. We demonstrate this procedure can be considered simultaneously in patients undergoing ESG to aid in weight loss for fatty liver disease.

Value of radiomic analysis of data from magnetic resonance elastography for diagnosing fibrosis stages in patients with hepatitis B/C

To evaluate the value of radiomic analysis of data from MR elastography (MRE) for diagnosing stages of fibrosis in patients with chronic hepatitis B/C (CHB/CHC). MRE images from 140 CHB/CHC patients with pathologically proven F0–F4 hepatic fibrosis stages were retrospectively analyzed, which is approved by our Institutional Review Board (IRB). A total of 364 radiomic features were extracted from spin-echo echo planar imaging with three-dimensional postprocessing (EPI3D) and gradient recalled echo with two-dimensional postprocessing (GRE2D) MRE data, including histogram parameters (HPs), gray level co-occurrence matrix (GLCM), and gray level run length matrix. Feature selection (significance test and correlation analysis) and classification (logistic regression models) were performed to stage ≥ F1, ≥ F2, ≥ F3 and F4, with a leave-one-out-based cross-validation method. Receiver operating characteristic analysis including areas under the curves (AUCs) was performed. Univariate analysis showed the best-performing features for classifying fibrosis stages were HPs (AUC range 0.798–0.929 for EPI3D and 0.727–0.916 for GRE2D). In multivariate radiomic analysis, AUCs for diagnosing fibrosis of ≥ F1, ≥ F2, ≥ F3 and cirrhosis (F4) were 0.888, 0.934, 0.924 and 0.948 for EPI3D MRE, and 0.887, 0.867, 0.892 and 0.941 for GRE2D MRE, which were slightly higher than that of EPI and GRE stiffness for each fibrosis stage (EPI 0.816, 0.924, 0.870 and 0.918; GRE 0.882, 0.800, 0.865 and 0.911). The AUCs of the EPI3D model were significantly higher than GRE2D model for staging clinically significant fibrosis (0.934 vs 0.867, P = 0.030) and advanced fibrosis (0.924 vs 0.892, P = 0.029). Radiomic analysis of MRE facilitates fibrosis classification in CHB/CHC patients, especially for identifying intermediate fibrosis, with a higher diagnostic performance by the EPI3D MRE.

Noninvasive Imaging Modalities in Nonalcoholic Fatty Liver Disease: Where Do We Stand?

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Liver biopsy is the gold standard for diagnosis and staging of fibrosis in patients with NAFLD; however, it is invasive, costly, and may be associated with morbidity and even mortality, so is not suitable for screening the large number of individuals who are at risk of, or have, NAFLD. Therefore, there has been tremendous focus on finding noninvasive diagnostic modalities, including imaging. New imaging modalities are emerging and may potentially replace biopsy. This review discusses the different noninvasive imaging modalities for the assessment of NAFLD.

Liver Fibrosis Assessment with Diffusion-Weighted Imaging: Value of Liver Apparent Diffusion Coefficient Normalization Using the Spleen as a Reference Organ.

Liver fibrosis staging is of great clinical importance because it is used to assess the severity of the underlying chronic liver disease. Among various imaging-based methods, apparent diffusion coefficient (ADC) measurement using diffusion-weighted imaging (DWI) has the potential to be used as an imaging biomarker for liver fibrosis assessment. In this study, we investigated the usefulness of liver ADC normalization using the spleen as a reference organ in liver fibrosis staging with 66 patients who underwent liver magnetic resonance imaging (MRI), transient elastography (TE), and surgical resection of a hepatic mass. ADC values of the liver (ADCliver) and spleen were analyzed, and the spleen was used for ADCliver normalization (nADCliver). ADCliver showed a weak negative correlation with TE (r = −0.246; p = 0.047) and fibrosis stage (r = −0.269; p = 0.029), while n ADCliver showed a moderate negative correlation with TE (r = −0.504; p < 0.001) and fibrosis stage (r = −0.579; p < 0.001). AUC values for nADCliver (0.777–0.875) were higher than those for ADCliver for each stage of fibrosis (0.596–0.713, p = 0.037–0.157). AUC values for TE (0.726–0.884) and nADCliver were not statistically different. In conclusion, normalized liver ADC can be useful in diagnosing liver fibrosis stage in patients with variable DWI acquisitions.