Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients.

Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13; rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) and glucokinase regulatory protein (GCKR; rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy; n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0×10-4). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.

Close Correlation between Frailty and Depressive State in Chronic Liver Diseases.

BACKGROUND AND OBJECTIVES: Few data with regard to the relevance between depression and frailty in chronic liver disease (CLD) patients are currently available. We aimed to elucidate the relationship between frailty and depression as evaluated by the Beck Depression Inventory-2nd edition (BDI-II) in CLD patients (n = 340, median age = 65.0 years). METHODS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were met: body weight loss, exhaustion, muscle weakness, slow walking speed and low physical activity. Depressive state was defined as BDI-II score 11 or greater. RESULTS: Robust (frailty score = zero), prefrail (frailty score = one or two) and frailty were identified in 114 (33.5%), 182 (53.5%) and 44 (12.9%). The median BDI-II score was five. Depressive state was identified in 84 patients (24.7%). The median BDI-II scores in patients with robust, prefrail and frail traits were 2, 7 and 12.5 (robust vs. prefrail, p < 0.0001; prefrail vs. robust, p = 0.0003; robust vs. frail, p < 0.0001; overall p < 0.0001). The proportions of depressive state in patients with robust, prefrail and frail traits were 3.51%, 30.77% and 54.55% (robust vs. prefrail, p < 0.0001; prefrail vs. robust, p = 0.0046; robust vs. frail, p < 0.0001; overall p < 0.0001). BDI-II score significantly correlated with frailty score (rs = 0.5855, p < 0.0001). CONCLUSIONS: The close correlation between frailty and depression can be found in CLD. Preventing frailty in CLD should be approached both physiologically and psychologically.

Clinical implications of serum Wisteria floribunda agglutinin-positive Mac-2-binding protein in treatment-naïve chronic hepatitis B.

AIM: To examine the relationship between serum Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) levels and liver histological findings for patients with treatment naïve chronic hepatitis B (CHB). METHODS: A total of 189 treatment naïve-CHB patients were analyzed. We examined the effect of pretreatment serum WFA+ -M2BP levels on histological findings compared with other laboratory markers, including aspartate aminotransferase (AST) to platelet ratio index, Fibrosis-4 index, platelet count, AST to alanine aminotransferase (ALT) ratio, and hyaluronic acid as liver fibrosis markers, and AST value, ALT value, and serum interferon-γ-inducible protein-10 level as liver inflammation markers. RESULTS: The WFA+ -M2BP value ranged from 0.3 cut-off index (COI) to 12.9 COI (median value, 1.2 COI). The degree of liver fibrosis was significantly stratified according to WFA+ -M2BP level in each group except for groups F2 and F3 and the degree of liver inflammation activity was significantly stratified according to WFA+ -M2BP level in each group. For predicting F4, WFA+ -M2BP level yielded the highest area under the receiver operating characteristic curve (AUROC) with a level of 0.87 and for predicting advanced liver fibrosis (≥F3) and significant liver fibrosis (≥F2), WFA+ -M2BP level yielded the second highest AUROCs (both, 0.77) among six fibrotic markers. For predicting severe (A3) or significant liver inflammation activity (≥A2), AUROCs of WFA+ -M2BP level were 0.78 and 0.76. CONCLUSION: The WFA+ -M2BP level can be a useful marker for assessing liver histological findings in patients with treatment-naïve CHB, although it has several limitations.

Proposal of a predictive model for advanced fibrosis containing Wisteria floribunda agglutinin-positive Mac-2-binding protein in chronic hepatitis C.

AIM: We aimed to construct a predictive model for advanced fibrosis containing Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+ -M2BP) level in patients with chronic hepatitis C (CHC) and to validate its accuracy in an independent cohort. METHODS: A total of 386 patients with CHC were retrospectively analyzed. For the purpose of this study, we formed a training set (n = 210) and a validation set (n = 176). In the training set, we investigated variables linked to the presence of advanced fibrosis using univariate and multivariate analyses. We constructed a formula for predicting advanced fibrosis and validated its accuracy in the validation cohort. Receiver operating characteristic curve (ROC) analysis was carried out for calculating the area under the ROC (AUROC). RESULTS: In multivariate analyses, WFA+ -M2BP (P = 0.029) and prothrombin time (PT) (P = 0.018) were found to be significant predictive factors linked to the presence of advanced fibrosis; platelet count (P = 0.098) and hyaluronic acid (P = 0.078) showed borderline statistical significance for the presence of advanced fibrosis. Using these four variables (with the initials MPPH), we constructed the following formula: MPPH score = -3.584 - (0.275 × WFA+ -M2BP) + (0.068 × platelet count) + (0.042 × PT) - (0.005 × hyaluronic acid). In the training and validation sets, MPPH score yielded the highest AUROCs (0.87 and 0.83) for predicting advanced fibrosis among eight serum liver fibrosis markers. Similarly, in the training and validation sets, MPPH score had the highest diagnostic accuracies for predicting advanced fibrosis among eight serum variables (81.4% and 74.4%). CONCLUSION: Our proposed MPPH scoring system can be useful for predicting advanced fibrosis in patients with CHC.

Clinical implication of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level on hepatitis B e-antigen loss or seroconversion in hepatitis B e-antigen positive patients.

AIM: To examine the impact of pretreatment Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+ -M2BP) level on hepatitis B e-antigen (HBeAg) loss or HBeAg seroconversion (SC) for patients with nucleoside/nucleotide analog (NUC) therapy naive HBeAg positive chronic hepatitis B (CHB). METHODS: A total of 57 patients were analyzed. All subjects were initially treated with NUC. We examined the impact of pretreatment WFA+ -M2BP level on HBeAg loss and HBeAg SC using univariate and multivariate analyses. RESULTS: There were 36 men and 21 women (median age, 39 years). The WFA+ -M2BP cut-off index (COI) level ranged 0.43-12.9 (median, 1.55). WFA+ -M2BP level in patients with F3 or F4 was significantly higher than that with F0-F2. WFA+ -M2BP level in patients with A2 or 3 was significantly higher than that with A0 or 1. For all cases, the 1- and 3-year cumulative HBeAg loss rates were 10.5% and 34.4% and the corresponding cumulative HBeAg SC rates were 8.8% and 29.0%, respectively. In the multivariate analysis, in terms of HBeAg loss, pretreatment HBV DNA of 5 log copies/mL or more and pretreatment WFA+ -M2BP level of more than 1.55 COI tended to be significant factors linked to loss of HBeAg, while in terms of HBeAg SC, pretreatment HBV DNA of 5 log copies/mL or more was an independent predictor and pretreatment WFA+ -M2BP level of more than 1.55 COI tended to be a significant factor. CONCLUSION: Pretreatment WFA+ -M2BP level may be a useful predictor for HBeAg loss or SC after NUC therapy for patients with HBeAg positive CHB.

Clinical significance of serum Wisteria floribunda agglutinin positive Mac-2-binding protein level in non-alcoholic steatohepatitis.

AIM: To examine the relationship between the Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+ -M2BP) level and histological findings for patients with non-alcoholic steatohepatitis (NASH). METHODS: A total of 134 NASH patients (mean age, 51.7 years) were analyzed. We examined the effect of WFA+ -M2BP level on severity of liver fibrosis comparing with other laboratory markers, including aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, AST to platelet ratio index (APRI), FIB-4 index, platelet count and hyaluronic acid as serum liver fibrosis markers. Receiver-operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC). RESULTS: The WFA+ -M2B P-value ranged from 0.2 cut-off index (COI) to 9.6 COI (median, 0.9). The median values in each fibrosis stage were: 0.7 COI in F1, 0.7 COI in F2, 1.2 COI in F3 and 2.4 COI in F4 (P < 0.001). For predicting liver cirrhosis (F4), WFA+ -M2BP level had the AUROC of 0.854 (sensitivity, 69.2%; specificity, 88.4%) and for predicting advanced liver fibrosis (≥F3), WFA+ -M2BP level yielded the second highest AUROC with a level of 0.842 (sensitivity, 73.7%; specificity, 80.2%) and for predicting significant liver fibrosis (≥F2), WFA+ -M2BP level yielded the highest AUROC with a level of 0.663 (sensitivity, 47.2%; specificity, 78.6%) among six liver fibrosis markers. The median values in patients with ballooning scores 1 (n = 58) and 2 (n = 76) were 0.6 and 1.1 COI, respectively (P < 0.001). CONCLUSION: Serum WFA+ -M2BP level can be useful for assessing liver histological findings in patients with NASH.

Comparison of sleep disorders in chronic hepatitis C patients treated with interferon-based therapy and direct acting antivirals using actigraphy.

This study aimed to compare the severity of sleep problems between chronic hepatitis C (CHC) patients treated with interferon (IFN)-based triple therapy (pegylated [Peg]-IFN plus ribavirin [RBV] plus simeprevir [SMV]) and those who received IFN-free direct-acting antiviral (DAA) therapy. METHODS: Our study included 31 patients in group A (Peg-IFN/RBV/SMV combination therapy) and 41 patients in the group B (IFN-free DAA therapy). We prospectively compared the effect of each antiviral treatment regimen on sleep conditions between the two groups adding actigraphy data. Five parameters detected by actigraphy (objective assessment) and scores of the Pittsburgh Sleep Quality Index (subjective assessment, n = 30 [group A] and 35 [group B]) were estimated. The causal effect of each therapy on sleep disturbances was evaluated at baseline and at 4 weeks after commencement of therapy. RESULTS: In terms of baseline characteristics, no significant differences between groups were found, except for hepatitis C virus genotype. In group A, sustained virological response 12 rate was 83.9% (26/31), whereas in group B it was 95.1% (39/41). In group A, each score of waking after sleep onset, activity index, wake episodes, and Pittsburgh Sleep Quality Index at 4 weeks significantly increased compared to those evaluated at baseline. In group B, scores of all variables except for sleep episodes at 4 weeks did not significantly change compared to those at baseline. CONCLUSION: Interferon-based triple therapy in patients with CHC may cause significant sleep disturbances. Interferon-free DAA therapy is less likely to deteriorate sleep conditions in patients with CHC.

Possible Alterations in Appetite-related Molecules After the Elimination of Hepatitis C Virus.

BACKGROUND/AIM: Recent advances in antiviral treatment have achieved a sustained viral response (SVR) in over 95% of hepatitis C virus (HCV) infections. HCV elimination is suggested to improve several lifestyle-related factors; however, few studies have focused on dietary habit-/appetite-related factors. PATIENTS AND METHODS: HCV-infected patients who received Daclatasvir/Asnaprevir (DCV/ASV) therapy were enrolled, and the changes in appetite-related molecules after antiviral therapy were assessed with a multiple cytokine-measuring system. RESULTS: Among 119 HCV-infected patients who received DCV/ASV treatment, 104 (87.3%) achieved an SVR. In the SVR group, DCV/ASV treatment improved several liver-related variables at 24 weeks after the completion of therapy. In patients with an SVR, the values of glucagon-like peptide 1 (GLP-1) and leptin were significantly increased at 24 weeks after completing direct-acting antiviral therapy. However, no significant change was observed in non-SVR patients, regardless of the receipt of direct-acting antiviral treatment. CONCLUSION: Gastrointestinal hormones related to the dietary habit and/or appetite may be influenced by HCV elimination.

Arm Skeletal Muscle Mass Is Associated With the Prognosis of Patients With Cirrhosis.

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/height2) and leg (leg skeletal mass muscle/height2) 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.

Association of an Overhydrated State With the Liver Fibrosis and Prognosis of Cirrhotic Patients.

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.

Calf Circumference as a Useful Predictor of Sarcopenia in Patients With Liver Diseases.

BACKGROUND/AIM: To elucidate the influence of calf circumference (CC) on sarcopenia in patients with chronic liver damages (CLDs, n=525, 255 men). PATIENTS AND METHODS: Anthropometry parameters including arm circumference, arm muscle circumference, CC, arm muscle area, triceps skinfold thickness, waist circumference and body mass index were measured. Patients with both grip strength (GS) decline and skeletal muscle index (SMI) decline were diagnosed as sarcopenic. RESULTS: Liver cirrhosis was identified in 103 cases (40.4%) in males and 87 cases (32.2%) in females. Sarcopenia was identified in 23 male patients (9.0%) and 38 female patients (14.1%). CC had the strong positive correlation with SMI both in male (r=0.79, p<0.0001) and female (r=0.83, p<0.0001). Among the above mentioned 7 anthropometry parameters, CC had the highest area under the receiver operating characteristics curve (AUC) for sarcopenia both in males (AUC=0.88) and females (AUC=0.86). CONCLUSION: CC can be helpful for predicting sarcopenia in CLDs.

Sarcopenia and Frailty in Chronic Liver Damage: Common and Different Points.

AIM: To elucidate the common and different points between sarcopenia and frailty in chronic liver damage (CLD). PATIENTS AND METHODS: Patients with both grip strength decline and skeletal muscle index decline were regarded as sarcopenia. Frailty was defined as a syndrome in which 3 or more of the following criteria were met: i) exhaustion, ii) body weight loss, iii) slow walking speed, iv) muscle weakness, and v) low physical activity. RESULTS: Sarcopenia and frailty were identified in 52 patients (15.2%) and 46 (13.5%), respectively. The prevalence of sarcopenia and frailty was well stratified according to age and the liver cirrhosis (LC) status. In the multivariate analysis, we identified significant factors for sarcopenia: i) age, ii) LC, iii) body mass index and iv) extracellular water (ECW) to total body water (TBW) ratio, while only the ECW to TBW ratio was significant for frailty. CONCLUSION: Sarcopenia and frailty in CLD should be separately evaluated.

Serum Zinc Level Is Associated with Frailty in Chronic Liver Diseases.

We sought to examine the serum zinc (Zn) level and frailty in patients with chronic liver diseases (CLDs, n = 285, 107 liver cirrhosis cases, median age = 66 years). Frailty was defined as a clinical syndrome in which three or more of the following criteria were met (frailty score 3, 4, or 5): unintentional body weight loss, self-reported exhaustion, muscle weakness (grip strength: <26 kg in men and <18 kg in women), slow walking speed (<1.0 m/s), and low physical activity. Robust (frailty score 0), prefrail (frailty score 1 or 2), and frailty were found in 90 (31.6%), 157 (55.1%), and 38 (13.3%), respectively. The median serum Zn levels in patients with frailty, prefrailty, and robust were 59.7 µg/dL, 72.8 µg/dL, and 76.9 µg/dL, respectively (p-values: frailty vs. prefrail, p < 0.0001; prefrail vs. robust, p = 0.0063; frailty vs. robust, p < 0.0001; overall p < 0.0001). For all cases, variables with absolute values of correlation coefficient with frailty score (0-5) ≥ 0.3 were age (rs = 0.3570, p < 0.0001), serum albumin (rs = -0.3212, p < 0.0001), extracellular water to total body water ratio using bioimpedance analysis (rs = 0.4386, p < 0.0001), and serum Zn level (rs = -0.3406, p < 0.0001). In conclusion, decreased serum Zn level in patients with CLDs can be closely associated with the presence of frailty.

Serum Zinc Level Grading System: A Useful Model for Composite Hepatic Events in Hepatitis C Virus-Associated Liver Cirrhosis.

We aimed to clarify the impact of the serum zinc (Zn) level grading system proposed by the Japanese society of clinical nutrition (JSCN: 80 µg/dL < serum Zn level <130 µg/dL (type A), 60 µg/dL < serum Zn level <80 µg/dL (type B), and serum Zn level <60 µg/dL (type C)) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC) on the incidence of composite hepatic events (Com-HEs) compared with Child-Pugh (C-P) classification or albumin-bilirubin (ALBI) grade. (n = 275, median age = 67 years). The Akaike information criterion (AIC) was compared among three prognostic models. Factors associated with the incidence of Com-HEs were also studied. The first incidence of any HE was confirmed in 112 patients (40.7%). The AIC value for Com-HEs by the Zn level grading system was the lowest among the three prognostic models (AIC: 301.788 in Zn level grading system, 303.372 in ALBI grade, and 333.953 in C-P classification). In the multivariate analysis, male (p = 0.0031), ALBI grade 3 (p = 0.0041), type B (p = 0.0238), type C (p = 0.0004), and persistent viremia (p < 0.0001) were significant factors associated with the incidence of Com-HEs. In conclusion, the serum Zn level grading system proposed by JSCN can be helpful for estimating the incidence of Com-HEs in HCV-related LC patients.

Health-Related Quality of Life and Frailty in Chronic Liver Diseases.

We sought to examine the relationship between frailty and health-related quality of life as evaluated using the 36-item Short-Form Health Survey (SF-36) questionnaire in Japanese chronic liver disease (CLD) patients (n = 341, 122 liver cirrhosis cases, median age = 66 years). Frailty was defined as a clinical syndrome in which three or more of the following criteria were met (frailty score 3, 4, or 5): unintentional body weight loss, self-reported exhaustion, muscle weakness (grip strength: <26 kg in men and <18 kg in women), slow walking speed (<1.0 m/s), and low physical activity. Robust (frailty score 0), prefrail (frailty score 1 or 2), and frailty were found in 108 (31.7%), 187 (54.8%), and 46 (13.5%) patients, respectively. In all eight scales of the SF-36 (physical functioning, role physical, bodily pain, general health perception, vitality, social functioning, role emotion, and mental health), and the physical component summary score and mental component summary score, each score was well stratified according to the frailty status (all p < 0.0001). In the multivariate analysis, age (p = 0.0126), physical functioning (p = 0.0005), and vitality (p = 0.0246) were independent predictors linked to the presence of frailty. In conclusion, Japanese CLD patients with frailty displayed poorer conditions, both physically and mentally.

Serum Zinc Level and non-Protein Respiratory Quotient in Patients with Chronic Liver Diseases.

We sought to clarify the correlation between non-protein respiratory quotient (npRQ) in indirect calorimetry and serum zinc (Zn) level in chronic liver diseases (CLDs, n = 586, 309 liver cirrhosis (LC) patients, median age = 63 years). Clinical parameters potentially linked to npRQ <0.85 (best cutoff point for the prognosis in LC patients) were also examined in receiver operating characteristic curve (ROC) analyses. The median npRQ was 0.86. The median serum Zn level was 64 µg/dL. The median npRQ in patients with non-LC, Child-Pugh A, Child-Pugh B and Child-Pugh C were 0.89, 0.85, 0.83 and 0.82 (overall p < 0.0001)). The median serum Zn level in patients with npRQ <0.85 (58 µg/dL) was significantly lower than that in patients with npRQ ≥ 0.85 (68 µg/dL) (p < 0.0001). The correlation coefficient (r) between npRQ level and serum Zn level for all cases was 0.40 (p < 0.0001). Similar tendencies were observed in all subgroup analyses. The highest correlation coefficient between serum Zn level and npRQ was found in patients with Child-Pugh C (n = 22, r = 0.69). In ROC analyses for npRQ <0.85, serum Zn level had the highest area under the ROC (AUC) among baseline laboratory parameters (AUC = 0.69). In conclusion, serum Zn level can be helpful for npRQ in patients with CLDs.

Prognostic significance of nonprotein respiratory quotient in patients with liver cirrhosis.

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.

Prediction of development of hepatocellular carcinoma using a new scoring system involving virtual touch quantification in patients with chronic liver diseases.

BACKGROUND: This study aimed to establish a new scoring system that combined several risk factors, including virtual touch quantification (VTQ) values and fasting plasma glucose (FPG) levels, for predicting the development of hepatocellular carcinoma (HCC) in patients with chronic liver disease. METHODS: A total of 1808 chronic liver disease patients who underwent VTQ measurement were analyzed. Risk factors for developing HCC were selected by multivariate Cox proportional hazards models. RESULTS: VTQ (>1.33 m/s), FPG (≥110 mg/dl), sex (male), age (≥55 years), and α-fetoprotein (AFP) level (≥5 ng/ml) were independently selected as risk factors for HCC development by multivariate analysis. Using these parameters, we established a new scoring system (0 to 5 points), based on VTQ, FPG, sex, age, and AFP level, named VFMAP. As compared with the low VFMAP score group (0 or 1 point), the hazard ratio for the incidence of HCC was 17.37 [95 % confidence interval (CI), 2.35-128.40] in the intermediate-score group (2 or 3 points) and 66.82 (95 % CI, 9.01-495.80) in the high-score group (4 or 5 points). The area under the receiver operating characteristic curve of the VFMAP score for predicting HCC development within 5 years was 0.82 (95 % CI, 0.76-0.87), indicating a moderate diagnostic value. A VFMAP cutoff value of 3 excluded HCC within 5 years with a high negative predictive value (98.2 %). CONCLUSION: The VFMAP score accurately predicted HCC in patients with chronic liver disease.

Effect of L-Carnitine in Patients With Liver Cirrhosis on Energy Metabolism Using Indirect Calorimetry: A Pilot Study.

BACKGROUND: L-carnitine supplementation has been suggested to show several favorable effects on patients with liver cirrhosis (LC). However, there have been no reports regarding the effect of L-carnitine on energy metabolism in patients with LC using indirect calorimetry which is a well-established method for assessing the degree of liver malnutrition. We examined the effect of L-carnitine in patients with LC on energy metabolism using indirect calorimetry. METHODS: A total of 13 LC patients who are scheduled to be treated with L-carnitine (1,800 mg/day) were analyzed in this study. None of the patients previously received L-carnitine. An evaluation of the nutritional status was performed at the initiation of L-carnitine therapy and after 4 weeks of L-carnitine therapy. We evaluated the effect of L-carnitine on the nutritional status and energy metabolism by comparing various clinical variables at these two time points. In addition, the changes in the nutritional status of the patients were also evaluated using indirect calorimetry. RESULTS: After 4 weeks of L-carnitine treatment, for all cases, the mean substrate oxidation rates of carbohydrate (%C) increased from 37.6% to 48.2%, the mean substrate oxidation rates of fat (%F) decreased from 40.2% to 31.9% and the mean substrate oxidation rates of protein (%P) decreased from 22.2% to 19.9%. In a subgroup analysis of patients with baseline non-protein respiratory quotient (npRQ) < 0.85, the mean %C increased from 15.3% to 34.2%, the mean %F decreased from 59.9% to 45.1%, and the mean %P decreased from 24.8% to 20.6%. After 4 weeks of L-carnitine treatment, for all cases (n = 13), the mean value of npRQ increased in comparison with the baseline levels, although the difference was not significant (0.868 ± 0.060 vs. 0.838 ± 0.097, P = 0.19). Conversely, in patients with baseline npRQ < 0.85, the npRQ value significantly increased after 4 weeks treatment of L-carnitine compared with the baseline levels (0.827 ± 0.030 vs. 0.760 ± 0.043, P = 0.016). CONCLUSION: L-carnitine supplementation can be useful for improving energy metabolism, especially in patients who have an advanced LC status and lower baseline npRQ values.

Factors Associated With Protein-energy Malnutrition in Chronic Liver Disease: Analysis Using Indirect Calorimetry.

We aimed to elucidate the incidence of protein-energy malnutrition (PEM) in patients with chronic liver disease and to identify factors linked to the presence of PEM.A total of 432 patients with chronic liver disease were analyzed in the current analysis. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient (npRQ) value using indirect calorimetry less than 0.85 as those with PEM. We compared between patients with PEM and those without PEM in baseline characteristics and examined factors linked to the presence of PEM using univariate and multivariate analyses.There are 216 patients with chronic hepatitis, 123 with Child-Pugh A, 80 with Child-Pugh B, and 13 with Child-Pugh C. Six patients (2.8%) had PEM in patients with chronic hepatitis, 17 (13.8%) in patients with Child-Pugh A, 42 (52.5%) in patients with Child-Pugh B, and 10 (76.9%) in patients with Child-Pugh C (P < 0.001). Multivariate analysis revealed that Child-Pugh classification (P < 0.001), age ≥64 years (P = 0.0428), aspartate aminotransferase (AST) ≥40 IU/L (P = 0.0023), and branched-chain amino acid to tyrosine ratio (BTR) ≤5.2 (P = 0.0328) were independent predictors linked to the presence of PEM. On the basis of numbers of above risk factors (age, AST, and BTR), the proportions of patients with PEM were well stratified especially in patients with early chronic hepatitis or Child-Pugh A (n = 339, P < 0.0001), while the proportions of patients with PEM tended to be well stratified in patients with Child-Pugh B or C (n = 93, P = 0.0673).Age, AST, and BTR can be useful markers for identifying PEM especially in patients with early stage of chronic liver disease.