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Background Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation. ClinicalTrials.gov Identifier: NCT04012242 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Yin in this issue.

Background: The relationship between liver fibrosis and inflammation and Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with chronic liver disease (CLD) other than hepatitis C remains uncertain, owing to the limitations of qualitative methods. Here, we evaluated the influence of liver fibrosis and inflammation on quantitative M2BPGi (M2BPGi-Qt) in CLD, considering each etiology., Methods: We recruited 1373 patients with CLD. To evaluate the influence of liver fibrosis and inflammation on M2BPGi-Qt levels, we assessed M2BPGi-Qt levels at each fibrosis and activity stage within different etiologies of CLD based on pathological findings. Subsequently, we evaluated if the accuracy of fibrosis staging based on M2BPGi-Qt could be improved by considering the influence of liver inflammation., Results: In patients with viral hepatitis, non-alcoholic fatty liver disease, and primary biliary cholangitis, the median M2BPGi-Qt levels increased liver fibrosis progression. Median M2BPGi-Qt levels were not associated with the degree of fibrosis in patients with autoimmune hepatitis (AIH). Median M2BPGi-Qt levels increased with the progression of liver activity in all etiologies. A significant difference was found at each stage in AIH. Considering the liver inflammation, we established an algorithm, M2BPGi-Qt, to determine the alanine aminotransferase-to-platelet ratio (MAP-R) in liver cirrhosis (LC). The area under the receiver operating characteristic curve (AUC) of MAP-R was higher than that of the M2BPGi-Qt for detecting LC (AUC MAP-R = 0.759 and M2BPGi-Qt = 0.700, p < 0.001)., Conclusions: The quantitative measurement system for M2BPGi depends on liver fibrosis and inflammation, regardless of etiology. Liver inflammation complicates the interpretation of M2BPGi-Qt results when assessing the fibrosis stage., (© 2024. Japanese Society of Gastroenterology.)

Background and Objectives : The geriatric nutritional risk index (GNRI) is an easily calculable index that can be determined using three common clinical variables. The GNRI is suggested to be related to sarcopenia in cirrhotic patients. However, the relationship between the GNRI and the prognosis in patients with liver cirrhosis (LC) has not been reported. The aim of the present research is to study the association of the GNRI with the nutritional status, hepatic function reserve, and prognosis in patients with liver cirrhosis (LC). Materials and Methods : A total of 370 cirrhotic patients whose nutritional statuses were evaluated using anthropometric measurements and bioimpedance analysis were studied. The associations between the GNRI and nutritional status and the GNRI and hepatic function reserve were analyzed. We also investigated the GNRI and prognosis of patients with LC. Results : The median age of the enrolled patients was 66 years old, and 266 (71.9%) patients had viral hepatitis-related LC. The GNRI was shown to decrease with the progression of chronic liver disease, represented by an increased FIB-4 index and severe Child-Pugh and mALBI grades. In addition, a low GNRI (<92) was associated with severe cirrhosis-related metabolic disorders, including a low branched-chain amino acid-to-tyrosine ratio (BTR) and a low zinc value. The GNRI was positively correlated with two nutrition-related anthropometric variables (% arm circumference and % arm muscle circumference), and a low GNRI was related to a low skeletal muscle mass index (SMI) (<7.0 kg/m 2 for men or <5.7 kg/m 2 for women), as determined by using bioimpedance analysis. In addition, patients with a low GNRI (<92) had a poorer prognosis than those with a high GNRI (≥92) (log-rank test: p = 0.0161, and generalized Wilcoxon test, p = 0.01261). Conclusions : Our results suggest that a low GNRI is related to severe chronic liver disease, low muscle volume, and a poor prognosis of patients with cirrhosis.

The picture of chronic liver diseases (CLDs) has changed considerably in recent years. One of them is the increase of non-alcoholic fatty liver disease. More and more CLD patients, even those with liver cirrhosis (LC), tend to be presenting with obesity these days. The annual rate of muscle loss increases with worsening liver reserve, and thus LC patients are more likely to complicate with sarcopenia. LC is also characterized by protein-energy malnutrition (PEM). Since the PEM in LC can be invariable, the patients probably present with sarcopenic obesity (Sa-O), which involves both sarcopenia and obesity. Currently, there is no mention of Sa-O in the guidelines; however, the rapidly increasing prevalence and poorer clinical consequences of Sa-O are recognized as an important public health problem, and the diagnostic value of Sa-O is expected to increase in the future. Sa-O involves a complex interplay of physiological mechanisms, including increased inflammatory cytokines, oxidative stress, insulin resistance, hormonal disorders, and decline of physical activity. The pathogenesis of Sa-O in LC is diverse, with a lot of perturbations in the muscle-liver-adipose tissue axis. Here, we overview the current knowledge of Sa-O, especially focusing on LC.

Background/aim: To elucidate factors associated with secular changes of grip strength (GS) in patients with chronic liver diseases (CLDs) (n=241, 102 males, median age=63 years, 87 liver cirrhosis cases)., Materials and Methods: ΔGS (kg/year) was defined as [GS value (second time) - GS value (first time)]/[time interval between the first and second time]. GS loss (GSL) was defined as ΔGS <0 kg/year., Results: The median ΔGS in patients with non-LC, Child-Pugh A (n=70) and Child-Pugh B (n=17) were 0.3, -0.2 and -1.6 kg/year (overall p<0.0001). In the multivariate analysis of factors linked to the GSL for all cases, extracellular water (ECW) to total body water (TBW) ratio was significant (p=0.0007). In the multivariate analysis in male, no significant factor was found, while in female, ECW to TBW ratio was significant (p=0.0024)., Conclusion: Liver functional parameters can be closely linked to the GSL especially in female CLD patients., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Sarcopenia in patients with liver cirrhosis (LC) has been attracting much attention these days because of the close linkage to adverse outcomes. LC can be related to secondary sarcopenia due to protein metabolic disorders and energy metabolic disorders. LC is associated with profound alterations in gut microbiota and injuries at the different levels of defensive mechanisms of the intestinal barrier. Dysbiosis refers to a state in which the diversity of gut microbiota is decreased by decreasing the bacterial species and the number of bacteria that compose the gut microbiota. The severe disturbance of intestinal barrier in LC can result in dysbiosis, several bacterial infections, LC-related complications, and sarcopenia. Here in this review, we will summarize the current knowledge of the relationship between sarcopenia and dysbiosis in patients with LC.

Background/aim: A bioimpedance analysis (BIA) can indicate an overhydrated state as the extracellular water/total body water (ECW/TBW) value. This study aimed to assess the clinical significance of this value in patients with chronic liver diseases (CLDs)., Patients and Methods: A total of 552 CLD patients who received a liver biopsy and underwent anthropometric assessment and BIA-based body composition analysis were enrolled. The association of the ECW/TBW value with the liver fibrosis and nutritional status was assessed. The relationship between the ECW/TBW value and the prognosis of cirrhotic patients (N=209) was also evaluated., Results: The ECW/TBW value increased as liver fibrosis progressed and was also related to decreased muscle mass/sarcopenia. The presence of overhydration was associated with a poor prognosis of cirrhotic patients., Conclusion: An increased ECW/TBW value was associated with progressive liver fibrosis and malnutrition and related to the prognosis of cirrhotic patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to assess the clinical significance of measuring the arm skeletal muscle mass in patients with cirrhosis., Patients and Methods: Using body composition data measured with the bioimpedance analysis (BIA) method, the skeletal muscle mass index (SMI) values of the arm (arm skeletal muscle mass/height 2 ) and leg (leg skeletal mass muscle/height 2 ) were calculated for 353 patients with cirrhosis, and the relationships of these indices to their prognosis were assessed. In addition, overhydration of the upper and lower limbs was compared., Results: Arm SMI was significantly positively associated with the prognosis of patients with cirrhosis (p=0.0002) but leg SMI was not (p=0.0829). The rate of overhydration in the lower limbs was significantly higher than that in the upper limbs (p<0.0001)., Conclusion: Arm SMI measured with the BIA method was suggested to be minimally affected by water retention, and might be clinically useful for patients with cirrhosis., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The bioimpedance analysis (BIA) can provide anthropometric data on patients. The aim of the study is to evaluate the clinical relevance of these automatically obtained values., Patients and Methods: We studied the arm circumference (AC) and arm muscle circumference (AMC) of 197 histologically proven cirrhotic patients. The BIA-based anthropometric data were compared to the manually measured data. In addition, we evaluated whether or not the BIA-based anthropometric data were associated with the prognosis of the patients., Results: The data of %AC and %AMC obtained using the two methods were well correlated (p<0.001) with relatively inconspicuous differences (approximately 6.0% for %AC and 16.0% for %AMC). The data of %AC and %AMC obtained from the BIA method were significantly associated with the prognosis of the patients., Conclusion: The BIA-based anthropometric data were associated with the direct measurement data and related to the prognosis of cirrhotic patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We aimed to compare the impact on survival among albumin-bilirubin (ALBI) grade, modified ALBI (mALBI) and our proposed combined ALBI grade and Mac-2 binding protein glycosylation isomer (M2BPGi) or FIB4 index grading system in chronic hepatitis C (CHC) related compensated liver cirrhosis (n = 165, 93 men and 72 women, median age = 67 years). Patients with ALBI grade 1, 2, and 3 were allocated a score of 1, 2, and 3 points, respectively. Patients with mALBI grade 1, 2A, and 2B were allocated a score of 1, 2, and 3 points, respectively. Patients with a high or low M2BPGi were allocated a score of 1 and 0 point. Patients with a high or low FIB4 index were allocated a score of 1 and 0 point. Sum of the point of ALBI (1, 2, or 3) and M2BPGi (0 or 1) or FIB4 index (0 or 1) was defined as ALBI-M2BPGi grade or ALBI-FIB4 grade. Prognostic accuracy was compared using the Akaike information criterion (AIC) value and time dependent receiver operating characteristics (ROC) curve analysis. The median follow-up duration was 5.422 years. AIC value for survival by ALBI-M2BPGi grade was the lowest among 4 prognostic models (AIC: 205.731 in ALBI grade, 200.913 in mALBI grade, 189.816 in ALBI-M2BPGi grade, and 204.671 in ALBI-FIB4 grade). All area under the ROC curves of ALBI-M2BPGi grade in each time point were higher than those of ALBI grade, mALBI grade, and ALBI-FIB4 grade. In conclusion, our proposed ALBI-M2BPGi grading system seems to be helpful for estimating prognosis in patients with CHC related compensated LC.

Aims: To identify the relationship between the Controlling Nutrition Status (CONUT) score and clinical parameters among adults with hepatitis C virus (HCV)-related liver cirrhosis (LC) ( n = 264, 141 males and 123 females)., Methods: The relationship between the CONUT score and clinical variables such as Child-Pugh classification were investigated. We also examined factors linked to poor nutritional state as determined by CONUT score., Results: According to the CONUT score, normal nutritional state was found in 57 patients, mild malnutrition state in 132, moderate malnutrition state in 68 and severe malnutrition state in 7. The CONUT score ranged from 0 to 9 (median = 2) in Child-Pugh A ( n = 198), 0 to 10 (median = 6) in Child-Pugh B ( n = 62) and 6 to 9 (median = 7.5) in Child-Pugh C ( n = 4) (overall, p < 0.00001). Multivariate analysis revealed that FIB-4 index, branched-chain amino acid to tyrosine ratio and extracellular water to total body water ratio in bioimpedance analysis were significant for both CONUT score 2 or more, and 5 or more. FIB-4 index had the highest predictability for both CONUT score 2 or more and 5 or more among three parameters., Conclusion: The CONUT score well reflects liver functional reserve among adults with HCV-related LC. FIB-4 index can be useful for malnutrition.

Due to varying positive rates of polymerase chain reaction (PCR) amplification, interpretation of conventional PCR results for non‑infectious ascites remains problematic. The present study developed a highly sensitive PCR protocol and investigated the positive rate of PCR for the 16S ribosomal (r)RNA gene in non‑infectious ascites. Following the design of a new PCR primer pair for the 16S rRNA gene (800F and 1400R), the sequences of PCR products were analyzed and the lower limit for bacterial DNA detection evaluated. The positive rate of PCR for 16S rRNA gene in non‑infectious ascites was also evaluated. PCR with the primer pair amplified the genomic DNA of 16S rRNA genes of major disease‑causing bacterial strains. Additionally, PCR with this primer pair provided highly sensitive detection of bacterial genomic DNA (lower limit, 0.1 pg of template DNA). When DNA samples isolated from ascites were used, the 16S rRNA gene was amplified independently of the presence of bacterial infection. PCR products contained the genomic DNA fragments of multiple bacterial species. Bacterial genomic DNA can be amplified from all ascitic fluids using a highly sensitive PCR protocol. Careful attention is required to interpret the results based on simple amplification of 16S rRNA gene with conventional PCR.

Aim: Whether direct-acting antiviral (DAA) therapy can reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus (HCV) infection remains unclear. We evaluated sequential changes in liver stiffness and steatosis using transient elastography (TE) and the TE-based controlled attenuation parameter (CAP) in patients with HCV who received DAA therapy., Patients and Methods: A total of 57 patients with HCV who received DAA therapy and achieved sustained virological response (SVR) were analyzed. Liver stiffness as evaluated with TE, steatosis as evaluated with CAP, and laboratory data were assessed before treatment (baseline), at end of treatment (EOT), 24 weeks after EOT (SVR24), and 48 weeks after EOT (SVR48)., Results: Alanine aminotransferase levels, corresponding to the presence of necroinflammatory activity, significantly decreased overall, with significant differences between baseline and EOT, EOT, and SVR24, and baseline and SVR48. However, alanine aminotransferase levels showed no significant changes between SVR24 and SVR48. Median (interquartile range) liver stiffness values at baseline, EOT, SVR24, and SVR48 were 8.3 (5.0-14.8), 7.4 (4.6-14.7), 5.3 (4.1-11.8), and 5.4 (4.0-13.4) kPa, respectively (baseline vs. EOT, P=0.044; EOT vs. SVR24, P=0.011; and SVR24 vs. SVR48, P=0.054). In patients with fatty liver (CAP≥236 dB/m, n=14), CAP values at baseline and SVR48 were 253 (245-278) and 229 (209-249) dB/m, respectively (P=0.020)., Conclusion: Liver stiffness at SVR24 might reflect liver fibrosis in the patients who received DAA therapy and achieved SVR. In addition, liver steatosis reduces in the same cohort with fatty liver.

Background: We aimed to elucidate the relationship between serum myostatin levels and other markers including skeletal muscle mass and to investigate the influence of serum myostatin levels on survival for patients with liver cirrhosis (LC)., Methods: A total of 198 LC subjects were analysed in this study. Myostatin levels were measured using stored sera. We retrospectively investigated the relationship between myostatin level and other markers, and the influence of myostatin level on overall survival (OS). Assessment of skeletal muscle mass was performed using the psoas muscle index (PMI) on computed tomography images at baseline. PMI indicates the sum of bilateral psoas muscle mass calculated by hand tracing at the lumber three level on computed tomography images divided by height squared (cm 2 /m 2 ). The study cohort was divided into two groups based on the median myostatin value in each gender., Results: Our study cohort included 108 male and 90 female patients with a median age of 67.5 years. The median (range) myostatin level for male patients was 3419.6 pg/mL (578.4-12897.7 pg/mL), whereas that for female patients was 2662.4 pg/mL (710.4-8782.0 pg/mL) (P = 0.0024). Median (range) serum myostatin level for Child-Pugh A patients (n = 123) was 2726.0 pg/mL (578.4-12667.2 pg/mL), whereas that for Child-Pugh B or C patients (n = 75) was 3615.2 pg/mL (663.3-12897.7 pg/mL) (P = 0.0011). For the entire cohort, the 1-, 3-, 5-, and 7-year cumulative OS rates were 93.94%, 72.71%, 50.37%, and 38.47%, respectively, in the high-myostatin group and 96.97%, 83.27%, 73.60%, and 69.95%, respectively, in the low-myostatin group (P = 0.0001). After excluding hepatocellular carcinoma patients (at baseline) from our analysis (n = 158), the 1-, 3-, 5-, and 7-year cumulative OS rates were 96.0%, 77.93%, 52.97%, and 39.08%, respectively, in the high-myostatin group and 96.39%, 87.58%, 77.63%, and 73.24%, respectively, in the low-myostatin group (P = 0.0005). Higher age (P = 0.0111) and lower PMI (P < 0.0001) were identified as significant predictors of poorer OS in our multivariate analysis, while higher serum myostatin (P = 0.0855) tended to be a significant adverse predictor. In both genders, PMI, serum albumin, prothrombin time, and branched-chain amino acid to tyrosine ratio showed a significantly inverse correlation with myostatin levels, and serum ammonia levels showed a significantly positive correlation with myostatin levels., Conclusions: Higher serum myostatin levels correlated with muscle mass loss, hyperammonemia, and impaired protein synthesis, as reflected by lower serum albumin levels and lower branched-chain amino acid to tyrosine ratio levels. High serum myostatin levels were also associated with a reduced OS rate in LC patients., (© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

We aimed to elucidate the relationship between serum liver fibrosis markers (Mac-2 binding protein glycosylation isomer (M2BPGi), FIB-4 index, aspartate aminotransferase to platelet ratio index and hyaluronic acid), and skeletal muscle mass and to investigate factors linked to skeletal muscle mass loss (SMML) in patients with chronic hepatitis C (CHC, n = 277, median age = 64 years). We defined patients with psoas muscle index [PMI, sum of bilateral psoas muscle mass calculated by manual trace method at the lumber 3 level on the computed tomography images divided by height squared (cm/m)] less than 6.36 cm/m for male and 3.92 cm/m for female as those with SMML based on the recommendations in current guidelines. Receiver operating curve (ROC) analysis was performed for predicting SMML in 4 liver fibrosis markers and parameters linked to SMML were also investigated in the univariate and multivariate analyses. In terms of liver fibrosis stages, F4 was observed in 115 patients, F3 in 67, F2 in 38, F1 in 53, and F0 in 4. The median (range) PMI for male and female were 6.198 (2.999-13.698) and 4.100 (1.691-7.052) cm/m, respectively. There were 72 male patients with SMML (55.4%) and 58 female patients with SMML (39.5%) (P = .0112). In both male and female, a significant inverse correlation between PMI and levels of liver fibrosis markers was observed in all liver fibrosis markers. ROC analyses for predicting SMML revealed that FIB-4 index had the highest area under the ROC (AUC = 0.712), followed by M2BPGi (AUC = 0.692). In the multivariate analysis of factors linked to SMML, gender (P = .0003), body mass index (P < .0001), FIB-4 index (P = .0039), and M2BPGi (P = .0121) were found to be significant predictors. In conclusion, liver fibrosis markers, especially FIB-4 index, can be helpful for predicting SMML in CHC patients.

Background: The objective of the present study was to examine the impact of muscle mass depletion (MMD) as determined by data in bioimpedance analysis (BIA) in liver cirrhosis (LC) patients (n = 382, 204 in male and 178 in female) on survival and to validate the utility of cutoff values in BIA recommended from current recommendations., Methods: Muscle mass depletion was defined as patients with skeletal muscle mass index (SMI) using BIA <7.0 cm 2 /m 2 for male and <5.7 cm 2 /m 2 for female based on current recommendations. We retrospectively examined variables related to the presence of MMD using univariate and multivariate analyses and investigated the impact of MMD on survival., Results: A total of 135 patients (35.3%) had MMD. Subjects were predominantly Child-Pugh A (278/382, 72.8%). For the entire cohort, the 5-year cumulative survival rates were 59.8% in patients with MMD and 84.4% in patients without MMD (P < 0.0001). In the multivariate analysis for survival, MMD revealed to be a significant adverse predictor for survival and for most subgroup analyses, the differences between MMD group and non-MMD group in terms of survival reached significance., Conclusion: Muscle mass measurement using BIA may be helpful for LC patients and current recommendations were well verified in our analysis., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Aims: To investigate the influence of skeletal muscle mass index (SMI) as determined by bioimpedance analysis (BIA) (appendicular skeletal muscle mass/(height)²) on survival by comparing the Child-Pugh score in patients with liver cirrhosis (LC, n = 383, average age = 65.2 years)., Patients and Methods: In terms of comparison of the effects of SMI and other markers on survival, we used time-dependent receiver operating characteristics (ROC) analysis., Results: The average SMI for male was 7.4 cm²/m² whereas that for female was 6.0 cm²/m² ( p < 0.0001). As for the Child-Pugh score, five points were in the majority, both in males (51.7%, (106/205)) and females (44.9%, (80/178)). For both genders, the survival curve was well stratified according to SMI ( p < 0.0001 for males and p = 0.0056 for females). In the multivariate analysis for survival, SMI and Child-Pugh scores were found to be significant both in males and females. In time-dependent ROC analyses, all area under the ROCs (AUROCs) for SMI in each time point were higher than those for Child-Pugh scores in males, while in females AUROCs for Child-Pugh scores at each time point were higher than those for SMI., Conclusion: SMI using BIA can be helpful for predicting outcomes, at least in male LC patients., Competing Interests: The authors declare no conflict of interest.

The aim of this study was to examine the effect of nonprotein respiratory quotient (npRQ), as assessed using indirect calorimetry, on clinical outcomes in patients with liver cirrhosis (LC). A total of 244 LC patients were evaluated in this study. For the univariate analysis, for each continuous variable, the optimal cutoff value that maximized the sum of sensitivity and specificity was selected using receiver operating curve (ROC) analysis for survival. There were 137 men and 107 women with the median (range) age of 67 (25-90) years. Indirect calorimetry indicated that 54 patients (22.1%) had hepatocellular carcinoma (HCC) on radiological findings and 59 patients (24.2%) had protein energy malnutrition, as defined by npRQ <0.85 and serum albumin level <3.5 g/dL. In ROC analysis of npRQ for survival, the optimal cutoff point of npRQ was 0.849 for all cases (area under the ROC = 0.61272; sensitivity, 66.22%; and specificity, 57.06%). The median follow-up periods after indirect calorimetry were 4.35 years (range, 1.01-9.66 years) in patients with npRQ ≥0.85 (n = 122) and 3.71 years (range, 0.19-9.51 years) in patients with npRQ <0.85 (n = 122). The 1-, 3-, and 5-year cumulative OS rates in patients with npRQ ≥0.85 were 100%, 87.79%, and 77.24%, respectively, whereas those in patients with npRQ <0.85 were 94.26%, 73.65% and 57.78%, respectively (P = 0.0004). In the multivariate analysis, presence of HCC (P = 0.0045), body mass index (P < 0.0001), serum albumin (P = 0.0441), prothrombin time (P = 0.0463), npRQ (P = 0.0024), estimated glomerular filtration rate (P = 0.0086), and des-γ-carboxy prothrombin (P = 0.0268) were found to be significant predictors associated with OS. For all cases, risk stratification for survival was well performed using these significant variables. In conclusion, npRQ value, as assessed by indirect calorimetry, can be helpful for predicting clinical outcomes for LC patients., Competing Interests: The authors have no conflicts of interest to disclose.

We aimed to examine the effect of Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA⁺-M2BP) level on survival comparing with other laboratory liver fibrosis markers in hepatitis C virus (HCV)-related compensated liver cirrhosis (LC) (n = 165). For assessing prognostic performance of continuous fibrosis markers, we adapted time-dependent receiver operating characteristics (ROC) curves for clinical outcome. In time-dependent ROC analysis, annual area under the ROCs (AUROCs) were plotted. We also calculated the total sum of AUROCs in all time-points (TAAT score) in each fibrosis marker. WFA⁺-M2BP value ranged from 0.66 cutoff index (COI) to 19.95 COI (median value, 5.29 COI). Using ROC analysis for survival, the optimal cutoff point for WFA⁺-M2BP was 6.15 COI (AUROC = 0.79348, sensitivity = 80.0%, specificity = 74.78%). The cumulative five-year survival rate in patients with WFA⁺-M2BP ≥ 6.15 COI (n = 69) was 43.99%, while that in patients with WFA⁺-M2BP < 6.15 COI (n = 96) was 88.40% (p < 0.0001). In the multivariate analysis, absence of hepatocellular carcinoma (p = 0.0008), WFA⁺-M2BP < 6.15 COI (p = 0.0132), achievement of sustained virological response (p < 0.0001) and des-γ-carboxy prothrombin < 41 mAU/mL (p = 0.0018) were significant favorable predictors linked to survival. In time-dependent ROC analysis in all cases, WFA⁺-M2BP had the highest TAAT score among liver fibrosis markers. In conclusion, WFA⁺-M2BP can be a useful predictor in HCV-related compensated LC., Competing Interests: The authors declare no conflict of interest.

We created a predictive model using serum-based biomarkers for advanced fibrosis (F3 or more) in patients with chronic hepatitis B (CHB) and to confirm the accuracy in an independent cohort.A total of 249 CHB patients were analyzed. To achieve our study aim, a training group (n = 125) and a validation group (n = 124) were formed. In the training group, parameters related to the presence of advanced fibrosis in univariate and multivariate analyses were examined, and a formula for advanced fibrosis was created. Next, we verified the applicability of the predictive model in the validation group.Multivariate analysis identified that gamma-glutamyl transpeptidase (GGT, P = 0.0343) and platelet count (P = 0.0034) were significant predictors of the presence of advanced fibrosis, while Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA-M2BP, P = 0.0741) and hyaluronic acid (P = 0.0916) tended to be significant factors. Using these 4 parameters, we created the following formula: GMPH score = -0.755 - (0.015 × GGT) - (0.268 × WFA-M2BP) + (0.167 × platelet count) + (0.003 × hyaluronic acid). In 8 analyzed variables (WFA-M2BP, aspartate aminotransferase-to-platelet ratio index, FIB-4 index, prothrombin time, platelet count, hyaluronic acid, Forns index, and GMPH score), GMPH score had the highest area under the receiver operating characteristic (AUROC) curve for advanced fibrosis with a value of 0.8064 in the training group and in the validation group, GMPH score also had the highest AUROC (0.7782). In all subgroup analyses of the hepatitis B virus (HBV) status (HB surface antigen quantification, HBV-DNA quantification, and HBe antigen seropositivity), GMPH score in F3 or F4 was significantly lower than that in F0 to F2. In the above mentioned 8 variables, differences between the liver fibrosis stages (F0 to F1 vs F2, F2 vs F3, F3 vs F4, F0 to F1 vs F3, F0 to F1 vs F4, and F2 vs F4) for the entire cohort (n = 249) were all significant only in GMPH score.In conclusion, the GMPH scoring system may be helpful for detecting advanced liver fibrosis in patients with CHB., Competing Interests: The authors have no conflicts of interest to disclose.

Background: This study aimed to examine the therapeutic effect and prognostic indicators of pegylated interferon (PEG-IFN) and ribavirin (RBV) combination therapy in thrombocytopenic patients with chronic hepatitis C, hepatitis C virus (HCV)-related cirrhosis, and those who underwent splenectomy or partial splenic embolization (PSE)., Methods: Of 326 patients with HCV-related chronic liver disease (252 with genotype 1b and 74 with genotype 2a/2b) treated with PEG-IFN/RBV, 90 were diagnosed with cirrhosis., Results: Regardless of the degree of thrombocytopenia, the administration rate was significantly higher in the splenectomy/PSE group compared to the cirrhosis group. However, in patients with genotype 1b, the sustained virological response (SVR) rate was significantly lower in the cirrhosis and the splenectomy/PSE groups compared to the chronic hepatitis group. No cirrhotic patients with platelets less than 80,000 achieved an SVR. Patients with genotype 2a/2b were more likely to achieve an SVR than genotype 1b. Prognostic factors for SVR in patients with genotype 1b included the absence of esophageal and gastric varices, high serum ALT, low AST/ALT ratio, and the major homo type of the IL28B gene. Splenectomy- or PSE-facilitated induction of IFN in patients with genotype 2a/2b was more likely to achieve an SVR by an IFN dose maintenance regimen. Patients with genotype 1b have a low SVR regardless of splenectomy/PSE. In particular, patients with a hetero/minor type of IL28B did not have an SVR., Conclusions: Splenectomy/PSE for IFN therapy should be performed in patients expected to achieve a treatment response, considering their genotype and IL28B.

Background: Acoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis., Aim: To evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography., Methods: A multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients., Results: The best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels>5 × the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively. Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively. For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa., Conclusion: Liver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The relationships between the metabolic parameters and the endoscopic findings of esophageal varices have been poorly investigated. We investigated the association of the branched-chain amino acids to tyrosine ratio (BTR) with the severity of liver fibrosis and esophageal varices., Material and Methods: We studied hepatitis C virus (HCV)-positive chronic liver disease patients who had undergone liver biopsy (n = 149). The relationship between the BTR values and the liver fibrotic stage was investigated. We also studied whether the BTR value was associated with the presence and bleeding risk of varices in patients with HCV-related compensated cirrhosis., Results: The mean values of the BTR decreased with the progression of the fibrosis (METAVIR score: F0-1: 6.40 ± 1.19; F2: 5.85 ± 1.33; F3: 5.24 ± 0.97, F4: 4.78 ± 1.14). In the 58 patients with HCV-related compensated cirrhosis, the mean values of the BTR decreased with the severity of varices (patients without varices: 5.01 ± 1.15, patients with a low-risk varices: 4.42 ± 1.06, patients with a high-risk varices: 3.86 ± 1.02). The BTR value was significantly lower in the patients with varices than in those without varices (4.17 ± 1.07 vs. 5.01 ± 1.15, P < 0.01). The BTR value was also significantly lower in the patients with a high risk of hemorrhage than in those with a low risk (3.86 ± 1.02 vs. 4.78 ± 1.14, P < 0.01). Furthermore, the BTR value was the most significantly different parameter, with the smallest P-value among all the factors examined, including the platelet count and albumin level., Conclusion: A decreased BTR value was found to be associated with the progression of liver fibrosis and severity of varices.

Aim: The aim of this international multicenter study was to evaluate the reliability of Acoustic Radiation Force Impulse (ARFI) elastography for predicting fibrosis severity, in patients with chronic hepatitis C., Patients and Methods: We compared ARFI to liver biopsy (LB) in 914 patients (10 centers, 5 countries) with chronic hepatitis C. In each patient LB (evaluated according to the METAVIR score) and ARFI measurements were performed (median of 5-10 valid measurements, expressed in meters/second - m/s). In 400 from the 914 patients, transient elastography (TE) was also performed (median of 6-10 valid measurements, expressed in kiloPascals - kPa)., Results: Valid ARFI measurements were obtained in 911 (99.6%) of 914 cases. On LB 61 cases (6.7%) had F0, 241 (26.4%) had F1, 202 (22.1%) had F2, 187 (20.4%) had F3, and 223 (24.4%) had F4 fibrosis. A highly significant correlation (r=0.654) was found between ARFI measurements and fibrosis (p<0.0001). The predictive values of ARFI for various stages of fibrosis were: F ≥ 1 - cut-off>1.19 m/s (AUROC=0.779), F ≥ 2 - cut-off>1.33 m/s (AUROC=0.792), F ≥ 3 - cut-off>1.43 m/s (AUROC=0.829), F=4 - cut-off>1.55 m/s (AUROC=0.842). The correlation with histological fibrosis was not significantly different for TE in comparison with ARFI elastography: r=0.728 vs. 0.689, p=0.28. TE was better than ARFI for predicting the presence of liver cirrhosis (p=0.01) and fibrosis (F ≥ 1, METAVIR) (p=0.01)., Conclusion: ARFI elastography is a reliable method for predicting fibrosis severity in chronic hepatitis C patients., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background/aims: Variceal hemorrhaging due to portal hypertension is a severe complication of liver cirrhosis. Although several biomarkers have been reported as predictors of the presence of varices, it is still difficult to assess the risk of variceal bleeding without esophagogastroduodenoscopy (EGD). The ratio of glycated albumin (GA) to glycated hemoglobin (HbA1c) was reported to increase with the progression of liver fibrosis. The aim of the study was to investigate whether the GA/HbA1c ratio is related to the severity and bleeding-risk of the varices., Methodology: We measured the GA/HbA1c ratio of HCV-related cirrhotic patients with Child-Pugh class A status and analyzed its relationship with the presence and bleeding risk of varices., Results: The GA/HbA1c ratio was higher in the patients who had the varices with a high risk of hemorrhage than in the patients with a low risk of bleeding. In addition, the GA/HbA1c ratio was higher in patients with varices than that in patients without varices. Furthermore, the GA/HbA1c ratio was the most significantly different parameter of all the factors examined, including the platelet count, prothrombin activity and albumin level., Conclusions: The GA/HbA1c ratio is increased in patients with varices and with the bleeding risk of the varices.

Objective: To evaluate the diagnostic accuracy of liver cirrhosis by imaging modalities, including CT, MRI and US, compared to results obtained from histopathological diagnoses of resected specimens., Materials and Methods: CT, MRI and US examinations of 142 patients with chronic liver disease who underwent surgery for complicated hepatocellular carcinoma (<3 cm in diameter) in 10 institutions were blindly reviewed in a multicenter study by three radiologists experienced in CT, MRI and US. The images were evaluated for five imaging parameters (irregular or nodular liver surface, blunt liver edge, liver parenchymal abnormalities, liver morphological changes and manifestations of portal hypertension) using a severity scale. The diagnostic imaging impression score was also calculated. Patients were histologically classified into chronic hepatitis (CH; n = 54), liver cirrhosis (LC; n = 71) and pre-cirrhosis (P-LC; n = 17) by three pathologists, independently, who reviewed the resected liver specimens. The results of the three imaging methods were compared to those from histological diagnoses, and a multivariate analysis (stepwise forward logistic regression analysis) was performed to identify independent predictive signs of cirrhosis. The diagnostic efficacies for LC and early cirrhosis were also compared among CT, MRI and US using a receiver-operating characteristic (ROC) curve analysis., Results: The differences in the five imaging parameters evaluated by CT, MRI and US between LC and CH were statistically significant (p < 0.001) except for the manifestations of portal hypertension on US. Irregular or nodular surface, blunt edge or morphological changes in the liver were selected as the best predictive signs for cirrhosis on US whereas liver parenchymal abnormalities, manifestations of portal hypertension and morphological changes in the liver were the best predictive signs on MRI and CT by multivariate analysis. The predictive diagnostic accuracy, sensitivity and specificity in discriminating LC from CH based on the best predictive signs were 71.9, 77.1 and 67.6% by CT; 67.9, 67.5 and 68.3% by MRI, and 66.0, 38.4 (lower than CT and MRI, p =0.001) and 88.8% (higher than CT and MRI, p =0.001)by US. According to the imaging impression scoring system, diagnostic accuracy, sensitivity and specificity were 67.0, 84.3 and 52.9% by CT; 70.3, 86.7 and 53.9% by MRI, and 64.0, 52.4 (lower than CT and MRI, p =0.0001) and 73.5% (higher than CT and MRI, p < 0.003) by US. ROC analysis showed that MRI and CT were slightly superior to US in the diagnosis of LC but no statistically significant difference was found between them. For the pathological diagnosis of P-LC, cirrhosis was diagnosed in 59.5, 46.7 and 41.7% of the P-LC cases by US, CT and MRI, respectively, with no significant difference among these methods., Conclusion: US, CT and MRI had different independent predictive signs for the diagnosis of LC. MRI and CT were slightly superior to US in predicting cirrhosis, especially regarding sensitivity. Noninvasive imaging techniques play an important role in the diagnosis of cirrhosis, especially in the evaluation of P-LC., (Copyright 2008 S. Karger AG, Basel.)